Trial Outcomes & Findings for A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies (NCT NCT02038777)
NCT ID: NCT02038777
Last Updated: 2025-02-26
Results Overview
Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
48 participants
Primary outcome timeframe
Day -5 up to Day 28 of Cycle 1 (33 days)
Results posted on
2025-02-26
Participant Flow
Total 54 participants signed the inform consent form (ICF). Out of which 6 participants were screen failure, 48 actually enrolled into the study and assigned to study treatment. One participant was randomized but not treated.
Participant milestones
| Measure |
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
Participants with advanced hematologic malignancies received PF-04449913 25 milligram (mg) tablets orally, a single dose on Day -5 of Cycle 1 and then continuously once daily (QD) from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
Participants with previously untreated acute myeloid leukemia (AML)/high-risk myelodysplastic syndrome (MDS) and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28 day cycles and low dose Ara-cytarabine (LDAC) 20 mg was administered subcutaneously (SC) twice daily for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first).
|
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg per square meter (mg/m\^2) was administered daily by continuous intravenous (IV) infusion for first 7 days of Cycle and Daunorubicin 60 mg/m\^2 daily IV for first 3 days of Cycle. Participants with \<= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m\^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles.
|
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m\^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28-day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
5
|
6
|
6
|
6
|
6
|
1
|
15
|
|
Overall Study
Treated (Safety Set)
|
3
|
4
|
6
|
6
|
6
|
6
|
1
|
15
|
|
Overall Study
COMPLETED
|
2
|
1
|
3
|
2
|
3
|
2
|
0
|
3
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
3
|
4
|
3
|
4
|
1
|
12
|
Reasons for withdrawal
| Measure |
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
Participants with advanced hematologic malignancies received PF-04449913 25 milligram (mg) tablets orally, a single dose on Day -5 of Cycle 1 and then continuously once daily (QD) from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
Participants with previously untreated acute myeloid leukemia (AML)/high-risk myelodysplastic syndrome (MDS) and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28 day cycles and low dose Ara-cytarabine (LDAC) 20 mg was administered subcutaneously (SC) twice daily for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first).
|
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg per square meter (mg/m\^2) was administered daily by continuous intravenous (IV) infusion for first 7 days of Cycle and Daunorubicin 60 mg/m\^2 daily IV for first 3 days of Cycle. Participants with \<= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28 day cycle along with Cytarabine 1g/m\^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles.
|
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m\^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28-day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
|---|---|---|---|---|---|---|---|---|
|
Overall Study
Death
|
0
|
2
|
0
|
1
|
2
|
4
|
0
|
11
|
|
Overall Study
Lost to Follow-up
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Other
|
0
|
1
|
0
|
2
|
1
|
0
|
0
|
0
|
|
Overall Study
Randomized but not treated
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
Started Chemotherapy
|
1
|
0
|
3
|
0
|
0
|
0
|
0
|
0
|
|
Overall Study
participation terminated by sponsor
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
Baseline Characteristics
A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies
Baseline characteristics by cohort
| Measure |
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
n=6 Participants
Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first).
|
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
n=6 Participants
Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m\^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m\^2 daily IV for first 3 days of Cycle. Participants with \<= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28-day cycle along with Cytarabine 1g/m\^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles.
|
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
n=6 Participants
Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m\^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
n=1 Participants
Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Total
n=47 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
59.3 Years
STANDARD_DEVIATION 9.07 • n=5 Participants
|
67.3 Years
STANDARD_DEVIATION 3.59 • n=7 Participants
|
70 Years
STANDARD_DEVIATION 8.53 • n=5 Participants
|
71.8 Years
STANDARD_DEVIATION 8.73 • n=4 Participants
|
68 Years
STANDARD_DEVIATION 4.94 • n=21 Participants
|
74.5 Years
STANDARD_DEVIATION 6.92 • n=8 Participants
|
77.0 Years
STANDARD_DEVIATION NA • n=8 Participants
|
77.5 Years
STANDARD_DEVIATION 5.21 • n=24 Participants
|
72.2 Years
STANDARD_DEVIATION 7.94 • n=42 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
2 Participants
n=21 Participants
|
2 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
7 Participants
n=24 Participants
|
18 Participants
n=42 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
8 Participants
n=24 Participants
|
29 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
15 Participants
n=24 Participants
|
47 Participants
n=42 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
1 Participants
n=8 Participants
|
15 Participants
n=24 Participants
|
47 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=8 Participants
|
0 Participants
n=24 Participants
|
0 Participants
n=42 Participants
|
PRIMARY outcome
Timeframe: Day -5 up to Day 28 of Cycle 1 (33 days)Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).
Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Dose-limiting Toxicities (DLTs): Monotherapy Cohort
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (For 25 mg: maximum up to 136 days; For 50 mg: maximum up to 179 days; For 100 mg: maximum up to 472 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE:any untoward medical occurrence at any dose that resulted in death;was life threatening;required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability/incapacity;resulted in congenital anomaly/birth defect. TEAEs:events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE:any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. National cancer institute common terminology criteria (NCI-CTCAE) Grade(G) v4.0:G 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G 4:life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort
TEAEs
|
3 Participants
|
4 Participants
|
6 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort
Serious TEAEs
|
1 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort
Treatment related TEAEs
|
1 Participants
|
3 Participants
|
5 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Monotherapy Cohort
Grade 3 or 4 TEAEs
|
2 Participants
|
1 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: For 25 mg: Baseline up to maximum 108 days; For 50 mg: Baseline up to maximum 151 days; For 100 mg: Baseline up to maximum 444 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Monotherapy Cohort
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: For 25 mg: Baseline up to maximum 136 days; For 50 mg: Baseline up to maximum 179 days; For 100 mg: Baseline up to maximum 472 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
Laboratory parameters included- hematology: lymphocytes/leukocytes percentage (%), neutrophils/leukocytes, basophils/leukocytes, eosinophils/leukocytes and monocytes/leukocytes (%), prothrombin time second (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase units per liter (u/l), protein gram/liter (g/l), blood urea nitrogen (BUN) millimoles per liter (mmol/l), urate, chloride, calcium (mmol/l); urinalysis: specific gravity, pH, urine glucose and ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low, abnormal high or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lymphocytes/Leukocytes · Abnormal low only
|
2 Participants
|
4 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Basophils/Leukocytes · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Basophils/Leukocytes · Abnormal high only
|
0 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Basophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Monocytes/Leukocytes · Normal
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Monocytes/Leukocytes · Abnormal low only
|
1 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Monocytes/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Prothrombin time · Normal
|
0 Participants
|
0 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Prothrombin time · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Prothrombin time · Abnormal high only
|
1 Participants
|
4 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Blasts/Leukocytes · Abnormal high only
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
BUN · Abnormal low only
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urate · Abnormal low only
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urate · Abnormal high only
|
0 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Chloride · Abnormal high only
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine specific gravity · Normal
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine specific gravity · Abnormal low only
|
0 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine specific gravity · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine pH · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine glucose · Normal
|
2 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine glucose · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine glucose · Abnormal high only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine ketones · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine ketones · Abnormal high only
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine nitrite · Normal
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine nitrite · Abnormal high only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocyte esterase · Normal
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Protein · Abnormal low only
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Chloride · Abnormal low only
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lymphocytes/Leukocytes · Normal
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lymphocytes/Leukocytes · Abnormal high only
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Protein · Abnormal high only
|
0 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lymphocytes/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Neutrophils/Leukocytes · Normal
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Neutrophils/Leukocytes · Abnormal low only
|
2 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Neutrophils/Leukocytes · Abnormal high only
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Neutrophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Basophils/Leukocytes · Normal
|
3 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Eosinophils/Leukocytes · Normal
|
3 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Eosinophils/Leukocytes · Abnormal low only
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Eosinophils/Leukocytes · Abnormal high only
|
0 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Eosinophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Monocytes/Leukocytes · Abnormal high only
|
0 Participants
|
2 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Prothrombin time · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Blasts/Leukocytes · Normal
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Blasts/Leukocytes · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Blasts/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lactate dehydrogenase · Normal
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Protein · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lactate dehydrogenase · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lactate dehydrogenase · Abnormal high only
|
3 Participants
|
4 Participants
|
5 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
BUN · Normal
|
0 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Lactate dehydrogenase · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
BUN · Abnormal high only
|
2 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
BUN · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urate · Normal
|
0 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Protein · Normal
|
1 Participants
|
0 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urate · Abnormal low and abnormal high
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Chloride · Normal
|
2 Participants
|
3 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Chloride · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Calcium · Normal
|
0 Participants
|
2 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Calcium · Abnormal low only
|
3 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Calcium · Abnormal high only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Calcium · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine specific gravity · Abnormal high only
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine pH · Normal
|
2 Participants
|
3 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine pH · Abnormal high only
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine pH · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine glucose · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine ketones · Normal
|
1 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine ketones · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine nitrite · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine nitrite · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocyte esterase · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocyte esterase · Abnormal high only
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocyte esterase · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine erythrocytes · Normal
|
2 Participants
|
2 Participants
|
4 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine erythrocytes · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine erythrocytes · Abnormal high only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine erythrocytes · Abnormal low and abnormal high
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocytes · Normal
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocytes · Abnormal low only
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Monotherapy Cohort
Urine leukocytes · Abnormal high only
|
1 Participants
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to Day 28 of Cycle 1 (28 days)Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).
Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With DLTs: Combination Cohort 1
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 514 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1
TEAEs
|
6 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1
Serious TEAEs
|
1 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1
Treatment Related TEAEs
|
6 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 1
Grade 3 or 4 TEAEs
|
4 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 486 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 1
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 514 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lymphocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Basophils/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Eosinophils/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Eosinophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Monocytes/Leukocytes · Abnormal low and abnormal high
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Blasts/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Blasts/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lactate dehydrogenase · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine specific gravity · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine nitrite · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine nitrite · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lymphocytes/Leukocytes · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lymphocytes/Leukocytes · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lymphocytes/Leukocytes · Abnormal low and abnormal high
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Neutrophils/Leukocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Neutrophils/Leukocytes · Abnormal low only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Neutrophils/Leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Neutrophils/Leukocytes · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Basophils/Leukocytes · Normal
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Basophils/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Basophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Eosinophils/Leukocytes · Normal
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Eosinophils/Leukocytes · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Monocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Monocytes/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Monocytes/Leukocytes · Abnormal high only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Prothrombin time · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Prothrombin time · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Prothrombin time · Abnormal high only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Prothrombin time · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Blasts/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Blasts/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lactate dehydrogenase · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lactate dehydrogenase · Abnormal high only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Lactate dehydrogenase · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Protein · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Protein · Abnormal low only
|
6 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Protein · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Protein · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
BUN · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
BUN · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
BUN · Abnormal high only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
BUN · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urate · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urate · Abnormal low only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urate · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urate · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Chloride · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Chloride · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Chloride · Abnormal high only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Chloride · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Calcium · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Calcium · Abnormal low only
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Calcium · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Calcium · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine specific gravity · Normal
|
6 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine specific gravity · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine specific gravity · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine pH · Normal
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine pH · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine pH · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine pH · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine glucose · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine glucose · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine glucose · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine glucose · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine ketones · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine ketones · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine ketones · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine ketones · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine nitrite · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine nitrite · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocyte esterase · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocyte esterase · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocyte esterase · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocyte esterase · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine erythrocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine erythrocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine erythrocytes · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine erythrocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocytes · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 1
Urine leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Day -3 up to anytime between Day 21 and Day 28 of first induction cycle (24 to 31 days)Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).
Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With DLTs: Combination Cohort 2
|
1 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 371 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2
Grade 3 or 4 TEAEs
|
4 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2
TEAEs
|
6 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2
Serious TEAEs
|
4 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 2
Treatment Related TEAEs
|
6 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 343 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 2
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 371 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here "number of participants analyzed" signifies participants evaluable for the specific parameter.
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Eosinophils/Leukocytes · Abnormal low and abnormal high
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Monocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Prothrombin time · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Prothrombin time · Abnormal high only
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Blasts/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Chloride · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Neutrophils/Leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Neutrophils/Leukocytes · Abnormal low and abnormal high
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Basophils/Leukocytes · Normal
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Basophils/Leukocytes · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Basophils/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Basophils/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Eosinophils/Leukocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Eosinophils/Leukocytes · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Eosinophils/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Monocytes/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Monocytes/Leukocytes · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Monocytes/Leukocytes · Abnormal low and abnormal high
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Prothrombin time · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Prothrombin time · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Blasts/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Blasts/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Blasts/Leukocytes · Abnormal high only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lactate dehydrogenase · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lactate dehydrogenase · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lactate dehydrogenase · Abnormal high only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lactate dehydrogenase · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Protein · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Protein · Abnormal low only
|
6 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Protein · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Protein · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
BUN · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
BUN · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
BUN · Abnormal high only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
BUN · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urate · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urate · Abnormal low only
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urate · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urate · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Chloride · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Chloride · Abnormal low only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Chloride · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Calcium · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Calcium · Abnormal low only
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Calcium · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Calcium · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine specific gravity · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine specific gravity · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine specific gravity · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine specific gravity · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine pH · Normal
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine pH · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine pH · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine pH · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine glucose · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine glucose · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine glucose · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine glucose · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine ketones · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine ketones · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine ketones · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine ketones · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine erythrocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine erythrocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine erythrocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine erythrocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine leukocytes · Normal
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Urine leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lymphocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lymphocytes/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lymphocytes/Leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Neutrophils/Leukocytes · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Lymphocytes/Leukocytes · Abnormal low and abnormal high
|
6 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 2
Neutrophils/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 736 daysPopulation: Full analysis set (FAS) included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
DMR included complete remission (CR), CR with incomplete blood count recovery (Cri), morphologic leukemia-free state (MLFS), marrow CR (mCR) and partial remission (PR). CR: \>=11 gram per deciliter (g/dL) hemoglobin (Hgb), \>=1\*10\^9 neutrophils (L), \>=100\*10\^9 platelets (L), 0% blasts, \<=5% bone marrow blasts (BMB), normal maturation of all cell lines, if had persistent dysplasia. . CRi: \<1000 neutrophils (mcL), \<100000 platelets (mcL), \<5% BMB, either neutrophils or platelets not recovered, no extramedullary disease (EMD). MLFS: 1000 neutrophils (mcL) and \<100000 platelets (mcL), \<5% BMB, neutrophils and platelets not recovered, flow cytometry negative, no EMD. PR: \>=1000 neutrophils (mcL), \>=100000 platelets (mcL), decrease to 5-25 and \>=50% decrease from start, Blasts \<=5% if Auer rod positive. mCR: hematologic improvement (HI) response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Percentage of Participants Achieving Disease Modifying Response (DMR): Expansion Cohort
|
46.7 Percentage of participants
Interval 24.4 to 70.0
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to Day 28 of Cycle 1 (28 days)Population: DLT evaluable analysis set included all enrolled participants who received at least 1 dose of study medication and who did not have major treatment deviations during first cycle (DLT observation period).
Criteria: Grade \>=3 non-hematologic toxicity (nht), except Grade \>=3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities, alanine aminotransferase (AT)/aspartate AT elevation that returned to Grade \<=1/baseline within 7 days, allergic reactions possibly related to PF-04449913 that led to discontinuation of study drug; Prolonged myelosuppression lasted \>42 days from point of detection = absolute neutrophil count \< 500/microliter or platelet count \<10\*10\^9/L with a normal bone marrow (\<5% blasts and no evidence of disease or dysplasia); Inability to deliver \>=80% of the planned study doses for all agents in a combination due to nht; Delay of \>28 days in receiving next scheduled cycle due to persisting nht; Asymptomatic participant with Grade \>=3 QTc prolongation required repeat testing, re-evaluation by qualified person, and correction of reversible causes for confirmation. Post-correction, if Grade 3 prolongation persisted, event was a DLT.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With DLTs: Combination Cohort 3
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (maximum up to 869 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3
TEAEs
|
6 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3
Serious TEAEs
|
1 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3
Treatment related TEAEs
|
6 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Combination Cohort 3
Grade 3 or 4 TEAEs
|
5 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 841 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Vital signs included blood pressure (sitting or supine) and heart rate. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs Abnormalities: Combination Cohort 3
|
0 Participants
|
—
|
—
|
PRIMARY outcome
Timeframe: Baseline up to maximum 869 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here "number of participants analyzed" signifies participants evaluable for the specific parameter.
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), BUN (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Participants that had both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Monocytes/Leukocytes · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Blasts/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Blasts/Leukocytes · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Blasts/Leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lactate dehydrogenase · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Chloride · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Chloride · Abnormal low only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Chloride · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine glucose · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Protein · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Protein · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
BUN · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
BUN · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
BUN · Abnormal high only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
BUN · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urate · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urate · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urate · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urate · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Chloride · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Calcium · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Calcium · Abnormal low only
|
6 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Calcium · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Calcium · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine specific gravity · Normal
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine specific gravity · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine specific gravity · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine specific gravity · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine pH · Normal
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine pH · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine pH · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine pH · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine glucose · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine glucose · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine glucose · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine ketones · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine ketones · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine ketones · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine ketones · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine nitrite · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine nitrite · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine nitrite · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine nitrite · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocyte esterase · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocyte esterase · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocyte esterase · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocyte esterase · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine erythrocytes · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine erythrocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine erythrocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine erythrocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocytes · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Urine leukocytes · Abnormal low and abnormal high
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lymphocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lymphocytes/Leukocytes · Abnormal low only
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lymphocytes/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lymphocytes/Leukocytes · Abnormal low and abnormal high
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Neutrophils/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Neutrophils/Leukocytes · Abnormal low only
|
5 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Neutrophils/Leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Neutrophils/Leukocytes · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Basophils/Leukocytes · Normal
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Basophils/Leukocytes · Abnormal low only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Basophils/Leukocytes · Abnormal high only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Basophils/Leukocytes · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Eosinophils/Leukocytes · Normal
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Eosinophils/Leukocytes · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Eosinophils/Leukocytes · Abnormal high only
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Eosinophils/Leukocytes · Abnormal low and abnormal high
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Monocytes/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Monocytes/Leukocytes · Abnormal high only
|
3 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Monocytes/Leukocytes · Abnormal low and abnormal high
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Blasts/Leukocytes · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lactate dehydrogenase · Normal
|
0 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lactate dehydrogenase · Abnormal low only
|
1 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Lactate dehydrogenase · Abnormal high only
|
4 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Protein · Normal
|
2 Participants
|
—
|
—
|
|
Number of Participants With Worst On-study Laboratory Abnormalities: Combination Cohort 3
Protein · Abnormal low only
|
4 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: Pharmacokinetic (PK) parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Maximum Observed Plasma Concentration (Cmax) of PF-04449913: Monotherapy Cohort
|
281.5 nanogram per milliliter
Geometric Coefficient of Variation 96
|
321.1 nanogram per milliliter
Geometric Coefficient of Variation 57
|
1019 nanogram per milliliter
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-04449913: Monotherapy Cohort
|
1.970 Hours
Interval 1.08 to 4.0
|
3.955 Hours
Interval 2.02 to 7.28
|
1.950 Hours
Interval 0.933 to 4.03
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Terminal Plasma Half-life (T1/2) of PF-04449913: Monotherapy Cohort
|
17.83 Hours
Standard Deviation 1.0214
|
30.70 Hours
Standard Deviation 5.7498
|
18.67 Hours
Standard Deviation 3.5359
|
SECONDARY outcome
Timeframe: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 of Cycle 1; AUClast and AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort
AUCinf
|
3374 Nanogram*hour per milliliter
Geometric Coefficient of Variation 68
|
9596 Nanogram*hour per milliliter
Geometric Coefficient of Variation 65
|
13160 Nanogram*hour per milliliter
Geometric Coefficient of Variation 20
|
|
Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort
AUCtau
|
2413 Nanogram*hour per milliliter
Geometric Coefficient of Variation 73
|
4499 Nanogram*hour per milliliter
Geometric Coefficient of Variation 51
|
8843 Nanogram*hour per milliliter
Geometric Coefficient of Variation 19
|
|
Single Dose- Area Under the Plasma Concentration Curve: From Time Zero to End of Dosing Interval (AUCtau), From Time Zero to Last Quantifiable Concentration (AUClast) and From Time Zero to Infinity (AUCinf) of PF-04449913 for Monotherapy Cohort
AUClast
|
3255 Nanogram*hour per milliliter
Geometric Coefficient of Variation 70
|
8911 Nanogram*hour per milliliter
Geometric Coefficient of Variation 63
|
12750 Nanogram*hour per milliliter
Geometric Coefficient of Variation 21
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort
|
7.415 Liter per hour
Geometric Coefficient of Variation 68
|
5.210 Liter per hour
Geometric Coefficient of Variation 65
|
7.599 Liter per hour
Geometric Coefficient of Variation 20
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameter of interest of any of the study drugs.
Vz/F was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Single Dose- Volume of Distribution (Vz/F) of PF-04449913: Monotherapy Cohort
|
190.5 Liter
Geometric Coefficient of Variation 62
|
227.8 Liter
Geometric Coefficient of Variation 49
|
201.5 Liter
Geometric Coefficient of Variation 20
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1; Cavg: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; Ctrough: Pre-dose on Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here "number of participants analyzed" signifies participants evaluable for the specific parameter.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort
Cmax
|
356.9 Nanogram per milliliter
Geometric Coefficient of Variation 90
|
542.2 Nanogram per milliliter
Geometric Coefficient of Variation 10
|
1330 Nanogram per milliliter
Geometric Coefficient of Variation 12
|
|
Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort
Cmin
|
84.94 Nanogram per milliliter
Geometric Coefficient of Variation 127
|
237.2 Nanogram per milliliter
Geometric Coefficient of Variation 36
|
333.9 Nanogram per milliliter
Geometric Coefficient of Variation 34
|
|
Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort
Cavg
|
190.5 Nanogram per milliliter
Geometric Coefficient of Variation 99
|
388.1 Nanogram per milliliter
Geometric Coefficient of Variation 14
|
645.8 Nanogram per milliliter
Geometric Coefficient of Variation 26
|
|
Multiple Dose Cmax, Minimum Observed Plasma Concentration (Cmin), Average Observed Plasma Concentration (Cavg), Trough Plasma Concentration (Ctrough) of PF-04449913: Monotherapy Cohort
Ctrough
|
87.87 Nanogram per milliliter
Geometric Coefficient of Variation 139
|
240.0 Nanogram per milliliter
Geometric Coefficient of Variation 37
|
342.9 Nanogram per milliliter
Geometric Coefficient of Variation 35
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing on Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of PF-04449913: Monotherapy Cohort
|
3.970 Hours
Interval 3.9 to 4.02
|
4.000 Hours
Interval 3.93 to 7.25
|
1.950 Hours
Interval 0.933 to 3.9
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUClast = area under the curve from time zero to last quantifiable concentration. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau of PF-04449913: Monotherapy Cohort
|
4561 Nanogram*hour per milliliter
Geometric Coefficient of Variation 99
|
9299 Nanogram*hour per milliliter
Geometric Coefficient of Variation 14
|
15480 Nanogram*hour per milliliter
Geometric Coefficient of Variation 26
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 8, and 24 hours post PF-04449913 dosing Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Clearance (CL/F) of PF-04449913: Monotherapy Cohort
|
5.467 Liter per hour
Geometric Coefficient of Variation 98
|
5.369 Liter per hour
Geometric Coefficient of Variation 14
|
6.452 Liter per hour
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day -5 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Rac was the observed accumulation ratio for AUCtau, determined as ratio of Day 21 AUCtau to Day -5 AUCtau. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Accumulation Ratio (Rac) of PF-04449913: Monotherapy Cohort
|
1.893 Ratio
Geometric Coefficient of Variation 40
|
2.076 Ratio
Geometric Coefficient of Variation 67
|
1.752 Ratio
Geometric Coefficient of Variation 25
|
SECONDARY outcome
Timeframe: AUCtau: 0 to 24, 24 to 48, 48 to 72 hours post PF-04449913 dosing on Day 21 of Cycle 1; AUCinf: Pre-dose and 0.5, 1, 2, 4, 8, 24, 48, 72 hours post PF-04449913 dosing on Day -5 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Rss = Ratio of Day 21 AUCtau to Day -5 AUCinf. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Steady State Accumulation Ratio (Rss) of PF-04449913: Monotherapy Cohort
|
1.355 Ratio
Geometric Coefficient of Variation 32
|
1.017 Ratio
Geometric Coefficient of Variation 85
|
1.176 Ratio
Geometric Coefficient of Variation 18
|
SECONDARY outcome
Timeframe: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here "number of participants analyzed" signifies participants evaluable for the specific parameter.
Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=2 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=3 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=5 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Monotherapy Cohort
|
1.170 Ratio
Standard Deviation 0.2769
|
1.588 Ratio
Standard Deviation 0.1773
|
1.695 Ratio
Standard Deviation 0.1108
|
SECONDARY outcome
Timeframe: Day 1 up to End of Treatment (25 mg: maximum up to 108 days; 50 mg: maximum up to 151 days; 100 mg: maximum up to 444 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "number of participants analyzed" signifies participants evaluable for the specified rows.
Best response observed for: CR, Cri, MLFS, PR, PRi, CytogeneticCR(CRc), MolecularCR(CRm). For AML-CR:neutrophils(nt) \[mcL\]\>=1000, platelets(pt)\[mcL\]\>=10\^5, BMB\<5%. CRi:nt(mcL)\<1000/pt(mcL)\<10\^5, BMB\<5%. MLFS:nt(mcL)1000 and pt(mcL)\<10\^5, BMB\<5%. PR:nt(mcL)\>=1000, pt(mcL)\>=10\^5, decrease to 5-25 and \>=50% decrease from start. PRi: nt\<1000, \<10\^5. CRc: nt(mcL)\>1,000, pt(mcL)\>10\^5, BMB\<5%. CRm: nt(mcL)\>1,000, pt(uL)\>10\^5, BMB\<5%. For myelodysplasia-CR: hemoglobin(Hgb)\[gram per deciliter{g/dL}\]\>=11, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, blasts0%, BMB\<=5%. mCR:\<=5% and decreased by \>=50% BMB. PR:decrease by\>=50% with \>5% BMB, CRc: disappearance of chromosomal abnormality, no new appearance, PRc:\>=50% reduced chromosomal abnormality. For myleofibrosis-CR: hgb(g/L)\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, All \<=ULN, BMB \<=5%. PR: hgb\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9. CML- PR: 1-35% Philadelphia chromosome(PC) positive(+) cells, CR:0% PC+ cells. Responses with at least 1 participant were reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 Participants
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 Participants
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Best Response: Monotherapy Cohort
Morphologic CRi: AML
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Morphologic CR: AML
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
MLFs: AML
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Stable disease: AML
|
1 Participants
|
1 Participants
|
2 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Treatment failure: AML
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Marrow complete remission: MDS
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Stable disease: MDS
|
1 Participants
|
1 Participants
|
1 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Disease progression: MDS
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Treatment failure: MDS
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Stable disease: CML
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants With Best Response: Monotherapy Cohort
Disease progression: CML
|
0 Participants
|
1 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle 1; Cavg: 0 to 24 hours post PF-04449913 dose on Day 10 and 21 of Cycle; Ctrough: Pre-dose on Day 10 and 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cmax: Cycle 1/Day 10
|
1172 Nanogram per milliliter
Geometric Coefficient of Variation 38
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cmin: Cycle 1/Day 10
|
317.6 Nanogram per milliliter
Geometric Coefficient of Variation 91
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cavg: Cycle 1/Day 10
|
648.3 Nanogram per milliliter
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Ctrough: Cycle 1/Day 10
|
330.7 Nanogram per milliliter
Geometric Coefficient of Variation 92
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cmax: Cycle 1/Day 21
|
1317 Nanogram per milliliter
Geometric Coefficient of Variation 86
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cmin: Cycle 1/Day 21
|
341.6 Nanogram per milliliter
Geometric Coefficient of Variation 172
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Cavg: Cycle 1/Day 21
|
670.5 Nanogram per milliliter
Geometric Coefficient of Variation 113
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 1
Ctrough: Cycle 1/Day 21
|
376.2 Nanogram per milliliter
Geometric Coefficient of Variation 142
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 1
Cycle 1/Day 10
|
3.950 Hours
Interval 1.0 to 4.05
|
—
|
—
|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 1
Cycle 1/Day 21
|
1.935 Hours
Interval 0.967 to 2.0
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
AUCtau was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 1
Cycle 1/Day 10
|
15560 Nanogram*hour per milliliter
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 1
Cycle 1/Day 21
|
16070 Nanogram*hour per milliliter
Geometric Coefficient of Variation 113
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.5, 1, 2, 4, 6 and 24 hours post PF-04449913 dose on Day 10 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 1
Cycle 1/Day 10
|
6.428 Liter per hour
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 1
Cycle 1/Day 21
|
6.223 Liter per hour
Geometric Coefficient of Variation 113
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dose on Day 2 and Day 10 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "number of participants analyzed" signifies participants evaluable for the specific timepoint.
LDAC= low dose ara-cytarabine/low dose cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Ctrough: Cycle 1/Day 2
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Ctrough was not estimable as the analyte was not detected for any participant.
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cmax: Cycle 1/Day 10
|
106.7 Nanogram per milliliter
Geometric Coefficient of Variation 29
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cavg: Cycle 1/Day 10
|
8.135 Nanogram per milliliter
Geometric Coefficient of Variation 18
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Ctrough: Cycle 1/Day 10
|
0.5903 Nanogram per milliliter
Geometric Coefficient of Variation 11
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cmax: Cycle 1/Day 2
|
82.88 Nanogram per milliliter
Geometric Coefficient of Variation 105
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cmin: Cycle 1/Day 2
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Cmin was not estimable as the analyte was not detected for any participant.
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cavg: Cycle 1/Day 2
|
6.511 Nanogram per milliliter
Geometric Coefficient of Variation 82
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Cytarabine: Combination Cohort 1
Cmin: Cycle 1/Day 10
|
0.5903 Nanogram per milliliter
Geometric Coefficient of Variation 11
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
LDAC= low dose ara-cytarabine/low dose cytarabine.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of Cytarabine: Combination Cohort 1
Cycle 1/Day 2
|
0.2500 Hours
Interval 0.233 to 0.25
|
—
|
—
|
|
Multiple Dose- Tmax of Cytarabine: Combination Cohort 1
Cycle 1/Day 10
|
0.2500 Hours
Interval 0.233 to 0.317
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
LDAC= low dose ara-cytarabine/low dose cytarabine. Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- T1/2 of Cytarabine: Combination Cohort 1
Cycle 1/Day 2
|
1.027 Hours
Standard Deviation 0.27844
|
—
|
—
|
|
Multiple Dose- T1/2 of Cytarabine: Combination Cohort 1
Cycle 1/Day 10
|
0.8618 Hours
Standard Deviation 0.029677
|
—
|
—
|
SECONDARY outcome
Timeframe: AUCinf: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; AUCtau: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of CyclePopulation: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
LDAC= low dose ara-cytarabine/low dose cytarabine. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 12 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1
AUCinf: Cycle 1/Day 2
|
78.37 Nanogram*hour per milliliter
Geometric Coefficient of Variation 80
|
—
|
—
|
|
Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1
AUCtau: Cycle 1/Day 2
|
77.97 Nanogram*hour per milliliter
Geometric Coefficient of Variation 82
|
—
|
—
|
|
Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1
AUCinf: Cycle 1/Day 10
|
97.34 Nanogram*hour per milliliter
Geometric Coefficient of Variation 18
|
—
|
—
|
|
Multiple Dose- AUCinf and AUCtau of Cytarabine: Combination Cohort 1
AUCtau: Cycle 1/Day 10
|
97.58 Nanogram*hour per milliliter
Geometric Coefficient of Variation 18
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Cavg: 0 to 12 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1; Ctrough: Pre-LDAC dosing on Day 2 and Day 10 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Ara-uridine was a metabolite of cytarabine. Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 12 hours. Ctrough = Pre-dose concentration, observed directly from data. Ara-uridine was a metabolite of cytarabine.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Cmax: Cycle 1/Day 2
|
371.6 Nanogram per milliliter
Geometric Coefficient of Variation 37
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Cmin: Cycle 1/Day 2
|
141.9 Nanogram per milliliter
Geometric Coefficient of Variation 61
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Ctrough: Cycle 1/Day 2
|
141.9 Nanogram per milliliter
Geometric Coefficient of Variation 61
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Cmax: Cycle 1/Day 10
|
454.3 Nanogram per milliliter
Geometric Coefficient of Variation 33
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Cmin: Cycle 1/Day 10
|
201.7 Nanogram per milliliter
Geometric Coefficient of Variation 61
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, and Ctrough of Ara-uridine: Combination Cohort 1
Ctrough: Cycle 1/Day 10
|
201.7 Nanogram per milliliter
Geometric Coefficient of Variation 61
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose and 0.25, 0.5, 1, 2, 4 and 6 hours post LDAC dosing on Day 2 and Day 10 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Ara-uridine was a metabolite of cytarabine.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of Ara-uridine: Combination Cohort 1
Cycle 1/Day 2
|
1.515 Hours
Interval 0.917 to 4.0
|
—
|
—
|
|
Multiple Dose- Tmax of Ara-uridine: Combination Cohort 1
Cycle 1/Day 10
|
2.000 Hours
Interval 1.92 to 4.05
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose, 0.5, 1, 6, and 24 hrs post dose on Day 3, 10 of induction Cycle (IC) 1 and 4 hrs post dose on Day 10 of IC 1; Cavg: 0 to 24 hrs post dose on Day 3 and Day 10 of IC 1; Ctrough: Pre dose on Day 3 and Day 10 of IC 1 (PF-04449913 Dose)Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cmax: Cycle 1/Day 3
|
1047 Nanogram per milliliter
Geometric Coefficient of Variation 40
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cmin: Cycle 1/Day 3
|
318.2 Nanogram per milliliter
Geometric Coefficient of Variation 53
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cavg: Cycle 1/Day 3
|
650.9 Nanogram per milliliter
Geometric Coefficient of Variation 46
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Ctrough: Cycle 1/Day 3
|
354.0 Nanogram per milliliter
Geometric Coefficient of Variation 47
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cmax: Cycle 1/Day 10
|
1181 Nanogram per milliliter
Geometric Coefficient of Variation 54
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cmin: Cycle 1/Day 10
|
356.1 Nanogram per milliliter
Geometric Coefficient of Variation 85
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Cavg: Cycle 1/Day 10
|
755.2 Nanogram per milliliter
Geometric Coefficient of Variation 58
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 2
Ctrough: Cycle 1/Day 10
|
359.5 Nanogram per milliliter
Geometric Coefficient of Variation 85
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of Induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of Induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 2
Cycle 1/Day 3
|
5.950 Hours
Interval 1.0 to 6.13
|
—
|
—
|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 2
Cycle 1/Day 10
|
5.065 Hours
Interval 3.98 to 6.03
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 2
Cycle 1/Day 3
|
15630 Nanogram*hour per milliliter
Geometric Coefficient of Variation 46
|
—
|
—
|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 2
Cycle 1/Day 10
|
18120 Nanogram*hour per milliliter
Geometric Coefficient of Variation 58
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.5, 1, 6, and 24 hours post PF-04449913 dosing on Day 3 of induction Cycle 1 and pre-dose, 0.5, 1, 4, 6, and 24 hours post PF-04449913 dosing on Day 10 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 2
Cycle 1/Day 3
|
6.401 Liter per hour
Geometric Coefficient of Variation 46
|
—
|
—
|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 2
Cycle 1/Day 10
|
5.523 Liter per hour
Geometric Coefficient of Variation 58
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2
Cmax
|
942.8 Nanogram per milliliter
Geometric Coefficient of Variation 35
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2
Cmin
|
2.589 Nanogram per milliliter
Geometric Coefficient of Variation 25
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2
Cavg
|
30.89 Nanogram per milliliter
Geometric Coefficient of Variation 27
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicin: Combination Cohort 2
Ctrough
|
2.673 Nanogram per milliliter
Geometric Coefficient of Variation 24
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of Daunorubicin: Combination Cohort 2
|
0.3585 Hours
Interval 0.25 to 0.5
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of at induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Terminal plasma half-life is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- T1/2 of Daunorubicin: Combination Cohort 2
|
7.297 Hours
Standard Deviation 0.65525
|
—
|
—
|
SECONDARY outcome
Timeframe: AUCinf: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1; AUCtau: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCinf and AUCtau of Daunorubicin: Combination Cohort 2
AUCinf
|
770.4 Nanogram*hour per milliliter
Geometric Coefficient of Variation 27
|
—
|
—
|
|
Multiple Dose- AUCinf and AUCtau of Daunorubicin: Combination Cohort 2
AUCtau
|
741.6 Nanogram*hour per milliliter
Geometric Coefficient of Variation 27
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle (IC) 1; Cavg: 0 to 24 hours post dose on Day 3 of IC 1; Ctrough: Pre-dose on Day 3 of IC 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data. Daunorubicinol was a metabolite of daunorubicin.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2
Cmax
|
244.4 Nanogram per milliliter
Geometric Coefficient of Variation 37
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2
Cmin
|
66.38 Nanogram per milliliter
Geometric Coefficient of Variation 21
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2
Cavg
|
116.7 Nanogram per milliliter
Geometric Coefficient of Variation 13
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Daunorubicinol: Combination Cohort 2
Ctrough
|
66.53 Nanogram per milliliter
Geometric Coefficient of Variation 21
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25 (mid-infusion), 0.5 (immediately prior to end of infusion), 1, 4, 6, 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Daunorubicinol was a metabolite of daunorubicin.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of Daunorubicinol: Combination Cohort 2
|
0.3585 Hours
Interval 0.25 to 0.5
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours post daunorubicin dosing on Day 3 of induction Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Daunorubicinol was a metabolite of daunorubicin. AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau of Daunorubicinol: Combination Cohort 2
|
2800 Nanogram*hour per milliliter
Geometric Coefficient of Variation 13
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=5 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Combination Cohort 1
|
1.835 Ratio
Standard Deviation 0.3597
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 21 of Cycle 1 (Unspecified- at any time on Day 21)Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, "number of participants analyzed" signifies participants evaluable for the specific parameter.
Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (mRNA, fresh tissue) at baseline to day 21 cycle 1 is reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=4 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Ratio of GLI1 Levels at Baseline to Day 21 Cycle1: Combination Cohort 2
|
1.666 Ratio
Standard Deviation 0.0797
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "number of participants analyzed" signifies participants evaluable for the specified rows.
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils \[mcL\] \>=1000, platelets(pt)\[mcL\] \>=10\^5, BMB \<5%. CRi: neutrophils (mcL) \<1000 or pt (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and pt (mcL) \<10\^5, BMB \<5%. PR: neutrophils (mcL) \>=1000, pt (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: neutrophils (mcL) \<1000 or pt (mcL) \<10\^5, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. CRc: neutrophils (mcL) \>1,000, pt (mcL) \>10\^6, BMB \<5%. CRm: neutrophils (mcL) \>1,000, pt (mcL) \>100,000, BMB \<5%. For participants with myelodysplastic syndrome (MDS), DMR- CR: \>=11 Hgb (g/dL), \>=1\*10\^9 neutrophils(L), \>=100\*10\^9 pt(L), 0% blasts, \<=5% BMB. mCR: HI response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB. Only those responses which had at least 1 participant were reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Best Response: Combination Cohort 1
Morphologic CR: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 1
Stable disease: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 1
Treatment failure: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 1
Stable disease: MDS
|
2 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 343 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for AML- CR:neutrophils(nt)\[mcL\] \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: nt(mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: nt(mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: nt(mcL) \>=1000, platelets (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: nt(mcL) \<1000 or platelets (mcL) \<100000, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. Cytogenetic CR (CRc): nt(mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. CRm: nt(mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. For participants with myelodysplastic syndrome (MDS), DMR was defined as - CR: \>=11 Hgb (g/dL), \>=1\*10\^9 nt(L), \>=100\*10\^9 platelets (L), 0% blasts, \<=5% BMB. mCR: HI response, \<=5% and decreased by \>=50% BMB. PR: decrease by \>=50% but still \>5% BMB. Only those responses which had at least 1 participant were reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Best Response: Combination Cohort 2
Morphologic CR: AML
|
3 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
Morphologic CRi: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
MLFs: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
PR: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
MR: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
Treatment failure: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
Relapse: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 2
Indeterminate: AML
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Percentage of Participants With Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR: Combination Cohort 1
CR/CRi
|
16.7 Percentage of participants
Interval 0.4 to 64.1
|
—
|
—
|
|
Percentage of Participants With Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR: Combination Cohort 1
DMR
|
16.7 Percentage of participants
Interval 0.4 to 64.1
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 1
Duration of DMR
|
15.3 Months
|
—
|
—
|
|
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 1
Duration of CR/CRi
|
13.9 Months
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 486 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, " Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Time to Response: Combination Cohort 1
Time to CR/CRi
|
2.1 Months
|
—
|
—
|
|
Time to Response: Combination Cohort 1
Time to DMR
|
0.8 Months
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose of study drug up to death or date of last contact (maximum up to 514 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
Overall survival was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Overall Survival: Combination Cohort 1
|
11.8 Months
Interval 1.9 to
Upper limit of CI could not be achieved due to less number of participants with event..
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose of study drug up to death or date of last contact (maximum up to 1408 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
OS was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Overall Survival (OS): Expansion Cohort
|
13.6 Months
Interval 3.8 to 18.8
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug up to disease progression (maximum duration of 1408 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
Best response observed for: CR, Cri, MLFS, PR, PRi, CytogeneticCR(CRc), MolecularCR(CRm). For AML-CR:neutrophils(nt) \[mcL\]\>=1000, platelets(pt)\[mcL\]\>=10\^5, BMB\<5%. CRi:nt(mcL)\<1000/pt(mcL)\<10\^5, BMB\<5%. MLFS:nt(mcL)1000 and pt(mcL)\<10\^5, BMB\<5%. PR:nt(mcL)\>=1000, pt(mcL)\>=10\^5, decrease to 5-25 and \>=50% decrease from start. PRi: nt\<1000, \<10\^5. CRc: nt(mcL)\>1,000, pt(mcL)\>10\^5, BMB\<5%. CRm: nt(mcL)\>1,000, pt(uL)\>10\^5, BMB\<5%. For myelodysplasia-CR: hemoglobin(Hgb)\[gram per deciliter{g/dL}\]\>=11, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, blasts0%, BMB\<=5%. mCR:\<=5% and decreased by \>=50% BMB. PR:decrease by\>=50% with \>5% BMB, CRc: disappearance of chromosomal abnormality, no new appearance, PRc:\>=50% reduced chromosomal abnormality. For myleofibrosis-CR: hgb(g/L)\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9, All \<=ULN, BMB \<=5%. PR: hgb\>=110, nt(L)\>=1\*10\^9, pt(L)\>=100\*10\^9. CML- PR: 1-35% Philadelphia chromosome(PC) positive(+) cells, CR:0% PC+ cells. Responses with at least 1 participant were reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Best Response: Expansion Cohort
Not evaluable: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
Morphologic CR: AML
|
6 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
Morphologic CRi: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
MLFs: AML
|
0 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
PR: AML
|
0 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
PRi: AML
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
MR: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
SD: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
Treatment failure: AML
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
Relapse: AML
|
0 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Expansion Cohort
Indeterminate: AML
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 1408 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Percentage of Participants With CR/CRi and DMR: Expansion Cohort
Percentage of participants with DMR
|
46.7 Percentage of Participants
Interval 21.3 to 73.4
|
—
|
—
|
|
Percentage of Participants With CR/CRi and DMR: Expansion Cohort
Percentage of participants with CR/CRi
|
46.7 Percentage of Participants
Interval 21.3 to 73.4
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 1408 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=7 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Duration of Response: Expansion Cohort
Duration of CR/CRi
|
9.5 Months
Interval 3.9 to
Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.
|
—
|
—
|
|
Duration of Response: Expansion Cohort
Duration of DMR
|
10.1 Months
Interval 3.9 to
Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 1408 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "Number of Participants Analyzed" signifies participants evaluable for this outcome measure.
The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=7 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Time to Response: Expansion Cohort
Time to CR/CRi
|
5.0 Months
Interval 0.9 to 5.9
|
—
|
—
|
|
Time to Response: Expansion Cohort
Time to DMR
|
2.3 Months
Interval 0.9 to 5.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, Day 21 of Cycle 1(Predose)Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, "Number of Participants analyzed" signifies participants evaluable for the specific parameter.
Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (Blood, mRNA) at baseline to day 21 cycle 1 is reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Ratio of GLI1 Levels at Baseline to Day 21 Cycle 1: Expansion Cohort
|
0.905 Ratio
Standard Deviation 0.4147
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax, Cmin: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Cavg: 0 to 24 hors post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1; Ctrough: Pre PF-04449913 dosing on Day 7 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants analyzed" signifies participants evaluable for the specific timepoint.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval, dosing interval was of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cmin: Cycle 1/Day 21
|
323.2 Nanogram per milliliter
Geometric Coefficient of Variation 46
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cavg: Cycle 1/Day 21
|
701.9 Nanogram per milliliter
Geometric Coefficient of Variation 44
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cmax: Cycle 1/Day 7
|
1387 Nanogram per milliliter
Geometric Coefficient of Variation 22
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cmin: Cycle 1/Day 7
|
414.1 Nanogram per milliliter
Geometric Coefficient of Variation 33
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cavg: Cycle 1/Day 7
|
834.6 Nanogram per milliliter
Geometric Coefficient of Variation 22
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Ctrough: Cycle 1/Day 7
|
526.3 Nanogram per milliliter
Geometric Coefficient of Variation 28
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Cmax: Cycle 1/Day 21
|
1218 Nanogram per milliliter
Geometric Coefficient of Variation 51
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of PF-04449913: Combination Cohort 3
Ctrough: Cycle 1/Day 21
|
347.5 Nanogram per milliliter
Geometric Coefficient of Variation 45
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of Participants analyzed" signifies participants evaluable for the specific timepoint.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 3
Cycle 1/Day 7
|
4.000 Hours
Interval 3.9 to 6.0
|
—
|
—
|
|
Multiple Dose- Tmax of PF-04449913: Combination Cohort 3
Cycle 1/Day 21
|
2.500 Hours
Interval 0.9 to 5.98
|
—
|
—
|
SECONDARY outcome
Timeframe: 0 to 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of participants analyzed" signifies participants evaluable for the specific timepoint.
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 3
Cycle 1/Day 7
|
20010 Nanogram*hour per milliliter
Geometric Coefficient of Variation 22
|
—
|
—
|
|
Multiple Dose- AUCtau of PF-04449913: Combination Cohort 3
Cycle 1/Day 21
|
16860 Nanogram*hour per milliliter
Geometric Coefficient of Variation 44
|
—
|
—
|
SECONDARY outcome
Timeframe: Pre-dose, 0.25, 1, 4, 6, 24 hours post PF-04449913 dosing on Day 7 and Day 21 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs. Here, "Number of participants analyzed" signifies participants evaluable for the specific timepoint.
CL/F was defined as apparent total clearance of the drug from plasma after oral administration. CL/F of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL/F obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 3
Cycle 1/Day 7
|
4.999 Liter per hour
Geometric Coefficient of Variation 22
|
—
|
—
|
|
Multiple Dose- CL/F of PF-04449913: Combination Cohort 3
Cycle 1/Day 21
|
5.936 Liter per hour
Geometric Coefficient of Variation 44
|
—
|
—
|
SECONDARY outcome
Timeframe: Cmax: 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 1/Cycle 1;Cmin: Pre-dose, 0.25, 0.5, 1, 2, 6 hrs post azacitidine dose on Day 7/Cycle 1;Cavg: 0 to 24 hrs post azacitidine dose on Day 7/Cycle 1;Ctrough:Pre azacitidine dose on Day 7/Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Cmax = Maximum plasma concentration, observed directly from data. Cmin = Minimum plasma concentration observed directly from data. Cavg = Average plasma concentration over the dosing interval of 24 hours. Ctrough = Pre-dose concentration, observed directly from data.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Cmax: Cycle 1/Day 1
|
1803 Nanogram per milliliter
Geometric Coefficient of Variation 60
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Cmax: Cycle 1/Day 7
|
1717 Nanogram per milliliter
Geometric Coefficient of Variation 49
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Cmin: Cycle 1/Day 7
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Cmin was not estimable as the analyte was not detected for any participant.
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Cavg: Cycle 1/Day 7
|
51.60 Nanogram per milliliter
Geometric Coefficient of Variation 30
|
—
|
—
|
|
Multiple Dose- Cmax, Cmin, Cavg, and Ctrough of Azacitidine: Combination Cohort 3
Ctrough: Cycle 1/Day 7
|
NA Nanogram per milliliter
Geometric Coefficient of Variation NA
Ctrough was not estimable as the analyte was not detected for any participant.
|
—
|
—
|
SECONDARY outcome
Timeframe: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing on Day 7 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- Tmax of Azacitidine: Combination Cohort 3
Day 1
|
0.2500 Hours
Interval 0.233 to 0.5
|
—
|
—
|
|
Multiple Dose- Tmax of Azacitidine: Combination Cohort 3
Day 7
|
0.2500 Hours
Interval 0.233 to 0.5
|
—
|
—
|
SECONDARY outcome
Timeframe: AUCinf: 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at Day 1 of Cycle 1 and pre-dose, 0.25, 0.5, 1, 2, and 6 hours post azacitidine dosing at 7 of Cycle 1; AUCtau: 0 to 24 hours post azacitidine dosing on Day 1 and 7 of Cycle 1Population: PK parameter analysis set included all treated participants with at least 1 PK parameters of interest of any of the study drugs.
AUCtau, was determined by linear/log trapezoidal method. For AUC, tau (dosing interval) was 24 hours. AUCinf = AUClast + (Clast/kel), where Clast = predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis, and where kel = terminal elimination phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3
AUCinf: Cycle 1/Day 7
|
1200 Nanogram*hour per milliliter
Geometric Coefficient of Variation 33
|
—
|
—
|
|
Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3
AUCtau: Cycle 1/Day 1
|
1200 Nanogram*hour per milliliter
Geometric Coefficient of Variation 28
|
—
|
—
|
|
Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3
AUCinf: Cycle 1/Day 1
|
910.9 Nanogram*hour per milliliter
Geometric Coefficient of Variation 39
|
—
|
—
|
|
Multiple Dose- AUCtau and AUCinf of Azacitidine: Combination Cohort 3
AUCtau: Cycle 1/Day 7
|
1241 Nanogram*hour per milliliter
Geometric Coefficient of Variation 30
|
—
|
—
|
SECONDARY outcome
Timeframe: First dose of study drug up to death or date of last contact (maximum up to 841 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
Overall survival was defined as the time from the date of first dose of study drug to the date of death due to any cause. Participants last known to be alive were censored at the date of last contact.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Overall Survival: Combination Cohort 3
|
30.3 Months
Interval 6.1 to
Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline, at the end of treatment (hours unspecified, any day maximum up to 841 days)Population: The PD analysis set included all enrolled participants who received at least 1 dose of PF-04449913 and had at least 1 pharmacodynamic parameter in active treatment period. Here, "Number of participants analyzed" signifies participants evaluable for the specific parameter.
Biomarker assessments were used to understand the in vivo mechanism of action of PF-04449913, as well as potential mechanisms of resistance. In this outcome measure ratio of GLI1 levels (Blood, mRNA) to end of treatment is reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Ratio of GLI1 Levels at Baseline to End of Treatment: Combination Cohort 3
|
0.776 Ratio
Standard Deviation NA
Standard deviation could not be estimated as there was only 1 participant evaluable.
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
Best response observed for: CR, Cri, MLFS, PR, PRi, CRc, CRm. Response criteria for participants with AML- CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, decrease to 5-25 and \>=50% decrease from start. PRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB decrease to 5-25 and \>=50% decrease from start. Minor Response: BMB \>=25% decrease from start. CRc: neutrophils (mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. CRm: neutrophils (mcL) \>1,000, platelets (mcL) \>100,000, BMB \<5%. Only those responses which had at least 1 participant were reported.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Best Response: Combination Cohort 3
PRi
|
1 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 3
Treatment failure
|
2 Participants
|
—
|
—
|
|
Number of Participants With Best Response: Combination Cohort 3
Morphologic CR
|
3 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1.
CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=6 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Percentage of Participants With CR/CRi and DMR: Combination Cohort 3
CR/Cri
|
50.0 Percentage of participants
Interval 11.8 to 88.2
|
—
|
—
|
|
Percentage of Participants With CR/CRi and DMR: Combination Cohort 3
DMR
|
50.0 Percentage of participants
Interval 11.8 to 88.2
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "Number of participants analyzed" signifies participants evaluable for this outcome measure.
Duration of response was the time from the date of first documentation of a CR/CRi and DMR to the date of first documentation of relapse after CR/CRi and DMR or death due to any cause. Duration of response data was censored on the date of the last adequate response assessment for participants who do not have an event (relapse or death). DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
Duration of CR/CRi
|
6.6 Months
Interval 5.6 to 11.1
|
—
|
—
|
|
Duration of Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
Duration of DMR
|
6.6 Months
Interval 5.6 to 19.8
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to end of treatment (maximum up to 841 days)Population: FAS included all enrolled participants who received at least 1 dose of study medication on or after Cycle 1/Day 1. Here, "Number of participants analyzed" signifies participants evaluable for this outcome measure.
The time from the date of first dose of study drug to the date of first documentation of a CR or CRi and DMR. DMR included CR, CRi, MLFS, mCR and PR. CR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, bone marrow blasts (BMB) \<5%. CRi: neutrophils (mcL) \<1000 or platelets (mcL) \<100000, BMB \<5%. MLFS: neutrophils (mcL) 1000 and platelets (mcL) \<100000, BMB \<5%. PR: neutrophils (mcL) \>=1000, platelets (mcL) \>=100000, BMB decrease to 5-25 and \>=50% decrease from start.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=3 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Time to Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
Time to CR/CRi
|
5.9 Months
Interval 5.8 to 11.5
|
—
|
—
|
|
Time to Complete Remission (CR) or CR With Incomplete Blood Count Recovery (CRi) and DMR Response: Combination Cohort 3
Time to DMR
|
5.8 Months
Interval 2.8 to 5.9
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to maximum 1146 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, "Number of participants analyzed" signifies participants evaluable for this outcome measure.
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), blood urea nitrogen (BUN) (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities: Continuation Cohort
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (Maximum up to 1436 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
AE:any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. Serious AE:any untoward medical occurrence at any dose that resulted in death,was life threatening,required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability/incapacity,resulted in congenital anomaly/birth defect. TEAEs:events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE:any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. National cancer institute common terminology criteria (NCI-CTCAE) Grade(G) v4.0:G 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; G 4:life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort
TEAEs
|
15 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort
Serious TEAEs
|
9 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort
Grade 3 or 4 TEAEs
|
12 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Expansion Cohort
Treatment related TEAEs
|
14 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to maximum 1436 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Vital signs included blood pressure (sitting or supine) and heart rate. Vital sign criteria included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP minimum \< 50 mmHg; Diastolic BP change from baseline: maximum decrease and increase \>=20 mmHg; heart rate \<40 and \>120 beats per minute. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Vital Signs: Expansion Cohort
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to maximum 1146 daysPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, "Number of participants analyzed" signifies participants evaluable for this outcome measure.
Vital signs included blood pressure (sitting or supine) and heart rate. Vital sign criteria included: Systolic BP: \<90 millimeter of mercury \[mmHg\]; Systolic BP change from baseline: maximum increase and decrease \>=30 mmHg; Diastolic BP minimum \< 50 mmHg; Diastolic BP change from baseline: maximum decrease and increase \>=20 mmHg; heart rate \<40 and \>120 beats per minute. Clinically significant changes in vital signs were determined by the investigator's discretion.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Clinically Significant Vital Signs: Continuation Cohort
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Day 1 up to 28 days after last dose of study drug (Maximum up to 1146 days)Population: Safety analysis set included all enrolled participants who received at least 1 dose of study medication. Here, "Number of participants analyzed" signifies participants evaluable for this outcome measure.
AE: any untoward medical occurrence in participant who received study drug or medical device without regard to possibility of causal relationship with the treatment or usage. Serious AE: any untoward medical occurrence at any dose that resulted in death; was life threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in congenital anomaly/birth defect. TEAEs: events absent before treatment or that worsened relative to pretreatment state. Treatment-related TEAE: any untoward medical occurrence attributed to study drug in a participant who received study drug. Relatedness to drug was assessed by the Investigator. NCI-CTCAE Grade: Grade 3=severe or medically significant but not immediately life-threatening, hospitalization or prolongation of existing hospitalization indicated, disabling, limiting self-care ADL; Grade 4= life-threatening consequence, urgent intervention indicated.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=1 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort
TEAEs
|
1 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort
Treatment Related TEAEs
|
1 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort
Grade 3 or 4 TEAEs
|
0 Participants
|
—
|
—
|
|
Number of Participants With TEAEs, Serious TEAEs, Treatment Related TEAEs, Grade 3 or 4 TEAEs Based on NCI CTCAE v4.0: Continuation Cohort
Serious TEAEs
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline up to maximum 1436 monthsPopulation: Safety analysis set included all enrolled participants who received at least 1 dose of study medication.
Laboratory parameters included- hematology: lymphocytes/leukocytes (%), neutrophils/leukocytes (%), basophils/leukocytes (%), eosinophils/leukocytes (%), monocytes/leukocytes (%), prothrombin time (sec), blasts/leukocytes (%); clinical chemistry: lactate dehydrogenase (u/l), protein (g/l), blood urea nitrogen (BUN) (mmol/l), urate (mmol/l), chloride (mmol/l), calcium (mmol/l); urinalysis: specific gravity (scalar), pH (scalar), urine glucose (scalar), ketones (scalar), nitrite, leukocyte esterase, urine erythrocytes (scalar), urine leukocytes (scalar). In this outcome measure participants for each laboratory parameter were evaluated as normal, abnormal low only, abnormal high only or abnormal low and an abnormal high. Laboratory values were as per laboratory normal ranges. Values above normal range = abnormal high and below range = abnormal low. Participants with both an abnormal low and an abnormal high value while on study were reported as 'Abnormal low and Abnormal high'.
Outcome measures
| Measure |
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 Participants
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test Abnormalities: Expansion Cohort
|
0 Participants
|
—
|
—
|
Adverse Events
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Monotherapy Cohort: PF-04449913 50 mg
Serious events: 3 serious events
Other events: 4 other events
Deaths: 2 deaths
Monotherapy Cohort: PF-04449913 100 mg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 5 deaths
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
Serious events: 4 serious events
Other events: 6 other events
Deaths: 2 deaths
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
Serious events: 1 serious events
Other events: 6 other events
Deaths: 4 deaths
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
Serious events: 9 serious events
Other events: 15 other events
Deaths: 11 deaths
Serious adverse events
| Measure |
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
n=3 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
n=6 participants at risk
Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first).
|
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
n=6 participants at risk
Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m\^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m\^2 daily IV for first 3 days of Cycle. Participants with \<= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28-day cycle along with Cytarabine 1g/m\^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles.
|
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
n=6 participants at risk
Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m\^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
n=1 participants at risk
Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 participants at risk
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
|---|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Gastric ulcer haemorrhage
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Disease progression
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pneumonia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma recurrent
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Enteritis infectious
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pneumonia bacterial
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pneumonia cytomegaloviral
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Acute lung injury
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
Other adverse events
| Measure |
Monotherapy Cohort: PF-04449913 (Glasdegib) 25 mg
n=3 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 25 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 50 mg
n=4 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 50 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Monotherapy Cohort: PF-04449913 100 mg
n=6 participants at risk
Participants with advanced hematologic malignancies received PF-04449913 100 mg tablets orally, a single dose on Day -5 of Cycle 1 and then continuously QD from Cycle 1/Day 1 in 28-day cycles, maximum up to 12 cycles or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity (whichever occurred first).
|
Combination Cohort 1 (Unfit Participants): PF-04449913 100 mg + LDAC 20 mg
n=6 participants at risk
Participants with previously untreated AML/high-risk MDS and unfit for intensive chemotherapy, received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 3 in 28- day cycles and LDAC 20 mg was administered SC BID for first 10 days of the 28-day cycles, maximum up to up to 12 cycles or until disease progression or relapse, or participant refusal, or unacceptable toxicity occurs (whichever occurred first).
|
Combination Cohort 2 (Fit Participants): PF-04449913 100 mg + Cytarabine + Daunorubicin
n=6 participants at risk
Participants with previously untreated AML/high-risk MDS and fit for intensive chemotherapy, participants started receiving PF-04449913 100 mg tablets QD from Day -3 up to Day 28 for first induction cycle and then continuously QD from Cycle 1/Day 1 in 28 day cycles for rest of treatment duration along with Cytarabine 100 mg/m\^2 was administered daily by continuous IV infusion for first 7 days of Cycle and Daunorubicin 60 mg/m\^2 daily IV for first 3 days of Cycle. Participants with \<= 5% bone marrow blasts had second cycle of induction. Participants achieving a complete response after the completion of induction therapy were eligible to begin consolidation cycles. During consolidation, participants received PF-04449913 100 mg tablets orally QD in 28-day cycle along with Cytarabine 1g/m\^2 QD on Day 1, 3 and 5 of 28 day cycle. Consolidation was of 2 to 4 cycles. Post-consolidation participants received PF-04449913 100 mg tablets orally QD in 28-day cycle for maintenance up to maximum of 6 cycles.
|
Combination Cohort 3: PF-04449913 100 mg + Azacitidine
n=6 participants at risk
Participants with untreated AML and eligible for non-intensive chemotherapy received PF-04449913 100 mg tablets orally, continuously QD from Cycle 1/Day 2 in 28 day cycles along with azacitidine 75 mg/m\^2/day SC or IV daily on Days 1-7 of each 28-day cycle. Treatment continued for at least 6 cycles, or until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Continuation Cohort (Monotherapy Cohort): PF-04449913 100 mg
n=1 participants at risk
Participants with myelofibrosis treated with PF-04449913 in B1371013 received the same dose (100 mg) of PF-04449913 as at the time of discontinuation from study B1371013 from Cycle 1/Day 1 until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
Expansion Cohort (Unfit Participants): PF-04449913 100 mg+ LDAC 20 mg
n=15 participants at risk
Participants with previously untreated AML or high-risk MDS and unfit for intensive chemotherapy received PF-04449913 100 mg tablets continuously QD from Cycle 1/Day 1 in 28-day cycles and LDAC 20 mg SC twice daily for first 10 days of the 28 day cycles, until disease progression or relapse, or participant withdrawal, or unacceptable toxicity, or death (whichever occurred first).
|
|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
4/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
10/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Disseminated intravascular coagulation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
4/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
46.7%
7/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
6/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
83.3%
5/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
6/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Eye disorders
Conjunctival haemorrhage
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Eye disorders
Dry eye
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Eye disorders
Eyelid ptosis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Angular cheilitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Aphthous ulcer
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
75.0%
3/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
40.0%
6/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Gastrointestinal disorder
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Nausea
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
4/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
83.3%
5/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
10/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Proctalgia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Rectal prolapse
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Chest pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Chills
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Fatigue
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Injection site reaction
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Malaise
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Medical device site ulcer
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Mucosal inflammation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Oedema
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Oedema peripheral
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Pyrexia
|
66.7%
2/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
75.0%
3/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
46.7%
7/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Hepatobiliary disorders
Hepatic function abnormal
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Hepatobiliary disorders
Liver disorder
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Bacterial infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Cystitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Device related infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Epstein-Barr virus infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Gingivitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Klebsiella sepsis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Nail infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Oesophageal candidiasis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pharyngitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pneumonia
|
66.7%
2/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pneumonia fungal
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Allergic transfusion reaction
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Arthropod sting
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Compression fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
46.7%
7/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Head injury
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Injection related reaction
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Oral contusion
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Scratch
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood creatine phosphokinase increased
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood creatinine increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood potassium decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood sodium decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood urea increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood zinc decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Electrocardiogram QT prolonged
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
46.7%
7/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Weight decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
White blood cell count decreased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
5/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
75.0%
3/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
4/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
46.7%
7/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Fluid retention
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Gout
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Iron overload
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Tumour lysis syndrome
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Vitamin B12 deficiency
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Zinc deficiency
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Cytarabine syndrome
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
75.0%
3/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Dysgeusia
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
75.0%
3/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
83.3%
5/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
66.7%
4/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
83.3%
5/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
40.0%
6/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Taste disorder
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Tremor
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Psychiatric disorders
Delirium
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Renal impairment
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Urinary incontinence
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Acne
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
20.0%
3/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Asteatosis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Cold sweat
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
100.0%
1/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
26.7%
4/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Eczema asteatotic
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Eczema nummular
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Erythema multiforme
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Miliaria
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
3/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Vascular disorders
Haematoma
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Vascular disorders
Hypertension
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
13.3%
2/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
6.7%
1/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Ear and labyrinth disorders
Auricular chondritis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Fibrin degradation products increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Hyperaesthesia teeth
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Small intestinal haemorrhage
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Catheter site pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
General disorders
Chest discomfort
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Bacteraemia
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Bronchitis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Enteritis infectious
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Folliculitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Infective tenosynovitis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Influenza
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Infusion site infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Laryngitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Nasopharyngitis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Periodontitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Pseudomembranous colitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Rhinitis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Infections and infestations
Skin infection
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Facial bones fracture
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Fibrin D dimer increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
International normalised ratio increased
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Investigations
Prothrombin time prolonged
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Nervous system disorders
Muscle spasticity
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Psychiatric disorders
Anxiety disorder
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Glycosuria
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
25.0%
1/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Decubitus ulcer
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
50.0%
2/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Skin and subcutaneous tissue disorders
Erythema nodosum
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Vascular disorders
Phlebitis
|
33.3%
1/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
33.3%
2/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
|
Vascular disorders
Subclavian vein thrombosis
|
0.00%
0/3 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/4 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
16.7%
1/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/6 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/1 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
0.00%
0/15 • Day 1 up to 28 days after last dose of study drug. Monotherapy cohort, a) 25 mg: maximum up to 136 days; b) 50 mg: maximum up to 179 days; c) 100 mg: maximum up to 472 days. Combination cohort 1: maximum up to 514 days. Combination cohort 2: maximum up to 371 days. Combination cohort 3: maximum up to 869 days. Expansion cohort: maximum up to 1436 days. Continuation cohort: Maximum up to 1146 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER