Trial Outcomes & Findings for A Study of the Effects of ALKS 4230 (Nemvaleukin Alfa) on Subjects With Solid Tumors (NCT NCT02799095)
NCT ID: NCT02799095
Last Updated: 2025-05-21
Results Overview
DLT was defined by any of following events possibly, probably, or definitely related to ALKS 4230: Grade 4 neutrophil count decreased (neutropenia); Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; Thrombocytopenia; Any Grade 3 cardiac or central nervous system toxicity; Liver transaminase elevation higher than 8\*upper limit of normal (ULN) or total bilirubin higher than 6\*ULN; Grade 4 hypoalbuminemia; Fever more than (\>) 40 degree Celsius (°C) sustained for \>24 hours; Hypotension required the use of pressors or prolonged hospitalization (\>48 hours) for hypotension requiring medical intervention; Grade 3 or higher electrolyte abnormalities; Increase in amylase or lipase; Grade 3 or higher nausea, vomiting, or diarrhea; Any other Grade 4 nonhematologic toxicity or any other Grade 3 non-hematologic toxicity; Any other toxicity or adverse event (AE) not defined above that resulted in participant removal from the study or discontinuation of dosing by the Investigator.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
243 participants
Primary outcome timeframe
Cycle 1 Day 1 through Cycle 2 Day 15 (Cycle 1 length = 14 days; Cycle 2 length= 21 days)
Results posted on
2025-05-21
Participant Flow
The study was conducted at 47 investigative sites in the United States, Spain, Canada, South Korea, Australia, Belgium, and Poland.
A total of 243 participants were enrolled in this 3-part study (Parts A, B and C) to receive nemvaleukin alfa (ALKS 4230) either as monotherapy or in combination with pembrolizumab. Selected participants (43) enrolled in Monotherapy Parts A and B, and who did not demonstrate clinical benefit were eligible to rollover to Combination Therapy Part C and were rolled over in Part C, Cohort 4.
Participant milestones
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 0.1 microgram per kilogram (mcg/kg) intravenous (IV) infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
Participants with renal cell carcinoma (RCC) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 + Safety Run-in: Nemvaleukin Alfa 3mcg/kg +Pembrolizumab 200mg
Participants with programmed death receptor-1/programmed death ligand-1 (PD-1/L1) unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rolled over from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
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Part A
STARTED
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5
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12
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7
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Part A
COMPLETED
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Part A
NOT COMPLETED
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Part B
STARTED
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47
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27
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0
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0
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0
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Part B
COMPLETED
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3
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1
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0
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Part B
NOT COMPLETED
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44
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26
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Part C
STARTED
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3
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42
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26
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26
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43
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3
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21
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2
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Part C
COMPLETED
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0
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0
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Part C
NOT COMPLETED
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41
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26
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22
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35
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1
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20
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2
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Reasons for withdrawal
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 0.1 microgram per kilogram (mcg/kg) intravenous (IV) infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
Participants with renal cell carcinoma (RCC) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 + Safety Run-in: Nemvaleukin Alfa 3mcg/kg +Pembrolizumab 200mg
Participants with programmed death receptor-1/programmed death ligand-1 (PD-1/L1) unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rolled over from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with non-small-cell lung cancer (NSCLC) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with squamous cell carcinoma of the head and neck (SCCHN) received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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Part A
Adverse Event
|
1
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0
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1
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4
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1
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Part A
Death
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0
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0
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0
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0
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0
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0
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3
|
0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Part A
Lost to Follow-up
|
0
|
1
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0
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0
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0
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0
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1
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Part A
Progressive Disease
|
3
|
3
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3
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2
|
2
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
|
0
|
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Part A
Clinical Progression
|
1
|
0
|
2
|
1
|
5
|
0
|
0
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0
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0
|
0
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0
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0
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0
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0
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0
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0
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0
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Part A
Protocol Deviation
|
0
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0
|
1
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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0
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Part A
Withdrawal by Subject
|
0
|
0
|
0
|
1
|
3
|
1
|
1
|
0
|
0
|
0
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0
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0
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0
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0
|
0
|
0
|
0
|
|
Part A
Rolled Over to Part C, Cohort 4
|
0
|
0
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0
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0
|
1
|
2
|
2
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
7
|
7
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B
Progressive Disease
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
10
|
7
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part B
Rolled Over to Part C, Cohort 4
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
26
|
12
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part C
Adverse Event
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
3
|
1
|
0
|
1
|
0
|
0
|
0
|
|
Part C
Death
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
7
|
5
|
6
|
8
|
1
|
8
|
1
|
|
Part C
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
1
|
1
|
3
|
0
|
0
|
0
|
|
Part C
Progressive Disease
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
13
|
2
|
0
|
1
|
0
|
0
|
0
|
|
Part C
Clinical Progression
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
3
|
0
|
0
|
1
|
0
|
0
|
0
|
|
Part C
Withdrawal by Subject
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
13
|
15
|
13
|
21
|
0
|
12
|
1
|
|
Part C
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Part C
Other
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
0
|
2
|
2
|
0
|
0
|
0
|
0
|
Baseline Characteristics
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
Baseline characteristics by cohort
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=47 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin 6 Alfa mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 + Safety Run-in: Nemvaleukin Alfa 3mcg/kg +Pembrolizumab 200mg
n=42 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=43 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Total
n=286 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Age, Customized
Part B · > 84 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part A · 18 to 64 years
|
5 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
5 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
28 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part A · 65 to 84 years
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
8 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
18 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part A · > 84 years
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part B · 18 to 64 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
20 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
10 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
30 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part B · 65 to 84 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
27 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
17 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
44 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part C · 18 to 64 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
30 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
20 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
15 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
18 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
11 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
96 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part C · 65 to 84 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
12 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
11 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
25 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
9 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
69 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Age, Customized
Part C · > 84 years
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part A · Female
|
1 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
7 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
19 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part A · Male
|
4 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
7 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
5 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
27 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part B · Female
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
22 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
25 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part B · Male
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
25 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
24 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
49 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part C · Female
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
28 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
12 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
13 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
18 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
7 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
81 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Sex: Female, Male
Part C · Male
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
14 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
14 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
13 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
25 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
14 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
85 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part A · Hispanic or Latino
|
1 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
2 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part A · Not Hispanic or Latino
|
4 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
7 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
8 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
12 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
44 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part A · Unknown or Not Reported
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part B · Hispanic or Latino
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part B · Not Hispanic or Latino
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
47 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
26 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
73 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part B · Unknown or Not Reported
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part C · Hispanic or Latino
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part C · Not Hispanic or Latino
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
40 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
25 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
24 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
42 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
20 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
159 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Ethnicity (NIH/OMB)
Part C · Unknown or Not Reported
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · American Indian or Alaska Native
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · Asian
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · Black or African American
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
4 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · White
|
5 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
4 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
8 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
10 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
41 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · More than one race
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part A · Unknown or Not Reported
|
0 Participants
n=5 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=4 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=8 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=12 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=7 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=46 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · American Indian or Alaska Native
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · Asian
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
5 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
6 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · Native Hawaiian or Other Pacific Islander
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · Black or African American
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · White
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
42 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
25 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
67 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · More than one race
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part B · Unknown or Not Reported
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=47 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=27 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=74 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · American Indian or Alaska Native
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · Asian
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · Native Hawaiian or Other Pacific Islander
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · Black or African American
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
7 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
15 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · White
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
34 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
20 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
22 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
40 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
3 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
18 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
142 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · More than one race
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
|
Race (NIH/OMB)
Part C · Unknown or Not Reported
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=42 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
2 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=26 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=43 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=3 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
1 Participants
n=21 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
0 Participants
n=2 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
6 Participants
n=166 Participants • Here, "Number Analyzed" signifies participants who were evaluable for specified parts.
|
PRIMARY outcome
Timeframe: Cycle 1 Day 1 through Cycle 2 Day 15 (Cycle 1 length = 14 days; Cycle 2 length= 21 days)Population: Safety population included all participants who received at least 1 dose of nemvaleukin alfa or pembrolizumab.
DLT was defined by any of following events possibly, probably, or definitely related to ALKS 4230: Grade 4 neutrophil count decreased (neutropenia); Febrile neutropenia; CTCAE Grade 4 thrombocytopenia; Thrombocytopenia; Any Grade 3 cardiac or central nervous system toxicity; Liver transaminase elevation higher than 8\*upper limit of normal (ULN) or total bilirubin higher than 6\*ULN; Grade 4 hypoalbuminemia; Fever more than (\>) 40 degree Celsius (°C) sustained for \>24 hours; Hypotension required the use of pressors or prolonged hospitalization (\>48 hours) for hypotension requiring medical intervention; Grade 3 or higher electrolyte abnormalities; Increase in amylase or lipase; Grade 3 or higher nausea, vomiting, or diarrhea; Any other Grade 4 nonhematologic toxicity or any other Grade 3 non-hematologic toxicity; Any other toxicity or adverse event (AE) not defined above that resulted in participant removal from the study or discontinuation of dosing by the Investigator.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part A: Number of Participants With Dose-limiting Toxicities (DLTs) Based on Common Terminology Criteria for Adverse Events (CTCAE)
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
3 Participants
|
0 Participants
|
1 Participants
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)Population: Safety population included all participants who received at least 1 dose of nemvaleukin alfa or pembrolizumab.
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=47 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=42 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=43 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B, and C: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
|
5 Participants
|
4 Participants
|
7 Participants
|
8 Participants
|
12 Participants
|
3 Participants
|
7 Participants
|
46 Participants
|
27 Participants
|
3 Participants
|
42 Participants
|
26 Participants
|
26 Participants
|
39 Participants
|
3 Participants
|
21 Participants
|
2 Participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)Population: Safety population included all participants who received at least 1 dose of nemvaleukin alfa or pembrolizumab.
TEAEs were defined as AEs that were newly occurring or worsening from the time of the first dose of study drug. Severity was graded according to the National Cancer Institute (NCI) CTCAE (version 4.03) where, Grade 1: Mild- asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: Moderate- minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental activities of daily living (ADL) Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4: Life-threatening consequences; urgent intervention indicated. Grade 5: Death related to AE. As planned, Grades 1 and 2 were combined for reporting.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=47 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=42 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=43 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
Participants With Grade 4 TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
12 Participants
|
5 Participants
|
0 Participants
|
4 Participants
|
5 Participants
|
5 Participants
|
4 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
—
|
|
Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
Participants With Grade 1 and 2 TEAEs
|
2 Participants
|
3 Participants
|
4 Participants
|
2 Participants
|
3 Participants
|
1 Participants
|
1 Participants
|
6 Participants
|
5 Participants
|
3 Participants
|
16 Participants
|
7 Participants
|
6 Participants
|
13 Participants
|
1 Participants
|
4 Participants
|
0 Participants
|
—
|
|
Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
Participants With Grade 3 TEAEs
|
3 Participants
|
1 Participants
|
3 Participants
|
6 Participants
|
8 Participants
|
2 Participants
|
3 Participants
|
28 Participants
|
16 Participants
|
0 Participants
|
19 Participants
|
14 Participants
|
15 Participants
|
21 Participants
|
1 Participants
|
16 Participants
|
1 Participants
|
—
|
|
Parts A, B, and C: Number of Participants With TEAEs by Severity Grading
Participants With Grade 5 TEAEs
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
—
|
PRIMARY outcome
Timeframe: From first dose of study drug up to 40.3 months for Part B and up to 50.5 months for Part CPopulation: The antitumor evaluable population consisted of participants who complete 2 cycles of therapy and had at least one follow-up scan.
ORR rate was defined as the percentage of participants with objective evidence of CR or PR based on RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<) 10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=46 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=22 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=36 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=22 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=21 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=39 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=3 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=18 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=2 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts B and C: Overall Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
|
8.7 percentage of participants
Interval 2.4 to 20.8
|
13.6 percentage of participants
Interval 2.9 to 34.9
|
0.0 percentage of participants
Interval 0.0 to 70.8
|
13.9 percentage of participants
Interval 4.7 to 29.5
|
0.0 percentage of participants
Interval 0.0 to 15.4
|
28.6 percentage of participants
Interval 11.3 to 52.2
|
7.7 percentage of participants
Interval 1.6 to 20.9
|
66.7 percentage of participants
Interval 9.4 to 99.2
|
11.1 percentage of participants
Interval 1.4 to 34.7
|
50.0 percentage of participants
Interval 1.3 to 98.7
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dosePopulation: The pharmacokinetic (PK) population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=45 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=35 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=25 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=43 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=20 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 0 hour
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.0137 nanograms per milliliter (ng/mL)
Standard Deviation 0.0917
|
0.0329 nanograms per milliliter (ng/mL)
Standard Deviation 0.171
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.0151 nanograms per milliliter (ng/mL)
Standard Deviation 0.0988
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 1 hour
|
1.36 nanograms per milliliter (ng/mL)
Standard Deviation 0.646
|
4.84 nanograms per milliliter (ng/mL)
Standard Deviation 0.806
|
17.3 nanograms per milliliter (ng/mL)
Standard Deviation 5.46
|
58.3 nanograms per milliliter (ng/mL)
Standard Deviation 11.8
|
94.6 nanograms per milliliter (ng/mL)
Standard Deviation 14.3
|
105 nanograms per milliliter (ng/mL)
Standard Deviation 27.7
|
102 nanograms per milliliter (ng/mL)
Standard Deviation 33.2
|
93.3 nanograms per milliliter (ng/mL)
Standard Deviation 34.9
|
106 nanograms per milliliter (ng/mL)
Standard Deviation 30.3
|
13.7 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
48.2 nanograms per milliliter (ng/mL)
Standard Deviation 13.7
|
51.5 nanograms per milliliter (ng/mL)
Standard Deviation 10.0
|
54.2 nanograms per milliliter (ng/mL)
Standard Deviation 14.2
|
47.8 nanograms per milliliter (ng/mL)
Standard Deviation 13.0
|
43.0 nanograms per milliliter (ng/mL)
Standard Deviation 27.4
|
117 nanograms per milliliter (ng/mL)
Standard Deviation 17.2
|
114 nanograms per milliliter (ng/mL)
Standard Deviation 29.2
|
120 nanograms per milliliter (ng/mL)
Standard Deviation 5.86
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 2 hours
|
0.889 nanograms per milliliter (ng/mL)
Standard Deviation 0.174
|
3.43 nanograms per milliliter (ng/mL)
Standard Deviation 0.797
|
12.6 nanograms per milliliter (ng/mL)
Standard Deviation 4.40
|
44.9 nanograms per milliliter (ng/mL)
Standard Deviation 14.5
|
74.5 nanograms per milliliter (ng/mL)
Standard Deviation 18.2
|
76.9 nanograms per milliliter (ng/mL)
Standard Deviation 23.3
|
85.9 nanograms per milliliter (ng/mL)
Standard Deviation 26.8
|
76.7 nanograms per milliliter (ng/mL)
Standard Deviation 26.5
|
87.9 nanograms per milliliter (ng/mL)
Standard Deviation 23.5
|
11.3 nanograms per milliliter (ng/mL)
Standard Deviation 1.39
|
35.6 nanograms per milliliter (ng/mL)
Standard Deviation 8.32
|
38.8 nanograms per milliliter (ng/mL)
Standard Deviation 9.33
|
38.3 nanograms per milliliter (ng/mL)
Standard Deviation 11.1
|
37.1 nanograms per milliliter (ng/mL)
Standard Deviation 10.5
|
35.6 nanograms per milliliter (ng/mL)
Standard Deviation 30.6
|
92.6 nanograms per milliliter (ng/mL)
Standard Deviation 16.1
|
84.4 nanograms per milliliter (ng/mL)
Standard Deviation 24.6
|
89.7 nanograms per milliliter (ng/mL)
Standard Deviation 5.33
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 8 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
1.27 nanograms per milliliter (ng/mL)
Standard Deviation 0.509
|
3.89 nanograms per milliliter (ng/mL)
Standard Deviation 1.58
|
6.93 nanograms per milliliter (ng/mL)
Standard Deviation 3.91
|
5.74 nanograms per milliliter (ng/mL)
Standard Deviation 0.0933
|
7.51 nanograms per milliliter (ng/mL)
Standard Deviation 3.23
|
7.94 nanograms per milliliter (ng/mL)
Standard Deviation 6.53
|
6.49 nanograms per milliliter (ng/mL)
Standard Deviation 2.96
|
1.47 nanograms per milliliter (ng/mL)
Standard Deviation 0.445
|
28.2 nanograms per milliliter (ng/mL)
Standard Deviation 64.5
|
3.33 nanograms per milliliter (ng/mL)
Standard Deviation 1.87
|
3.99 nanograms per milliliter (ng/mL)
Standard Deviation 1.69
|
3.94 nanograms per milliliter (ng/mL)
Standard Deviation 1.97
|
12.2 nanograms per milliliter (ng/mL)
Standard Deviation 19.7
|
4.98 nanograms per milliliter (ng/mL)
Standard Deviation 1.92
|
9.78 nanograms per milliliter (ng/mL)
Standard Deviation 5.22
|
8.47 nanograms per milliliter (ng/mL)
Standard Deviation 3.87
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 0.5 hour
|
2.24 nanograms per milliliter (ng/mL)
Standard Deviation 1.06
|
6.13 nanograms per milliliter (ng/mL)
Standard Deviation 0.653
|
20.1 nanograms per milliliter (ng/mL)
Standard Deviation 5.32
|
77.9 nanograms per milliliter (ng/mL)
Standard Deviation 15.5
|
109 nanograms per milliliter (ng/mL)
Standard Deviation 29.6
|
157 nanograms per milliliter (ng/mL)
Standard Deviation 56.8
|
148 nanograms per milliliter (ng/mL)
Standard Deviation 18.2
|
102 nanograms per milliliter (ng/mL)
Standard Deviation 36.1
|
131 nanograms per milliliter (ng/mL)
Standard Deviation 51.3
|
18.6 nanograms per milliliter (ng/mL)
Standard Deviation 3.94
|
67.1 nanograms per milliliter (ng/mL)
Standard Deviation 14.9
|
61.7 nanograms per milliliter (ng/mL)
Standard Deviation 13.4
|
71.5 nanograms per milliliter (ng/mL)
Standard Deviation 51.7
|
62.5 nanograms per milliliter (ng/mL)
Standard Deviation 20.2
|
48.9 nanograms per milliliter (ng/mL)
Standard Deviation 19.8
|
120 nanograms per milliliter (ng/mL)
Standard Deviation 6.24
|
131 nanograms per milliliter (ng/mL)
Standard Deviation 52.7
|
89.3 nanograms per milliliter (ng/mL)
Standard Deviation 2.71
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 1 hour
|
1.61 nanograms per milliliter (ng/mL)
Standard Deviation 0.265
|
5.67 nanograms per milliliter (ng/mL)
Standard Deviation 1.61
|
16.6 nanograms per milliliter (ng/mL)
Standard Deviation 3.84
|
58.8 nanograms per milliliter (ng/mL)
Standard Deviation 25.3
|
112 nanograms per milliliter (ng/mL)
Standard Deviation 24.5
|
132 nanograms per milliliter (ng/mL)
Standard Deviation 33.0
|
135 nanograms per milliliter (ng/mL)
Standard Deviation 33.9
|
101 nanograms per milliliter (ng/mL)
Standard Deviation 32.3
|
117 nanograms per milliliter (ng/mL)
Standard Deviation 19.9
|
17.4 nanograms per milliliter (ng/mL)
Standard Deviation 5.33
|
50.0 nanograms per milliliter (ng/mL)
Standard Deviation 22.3
|
56.3 nanograms per milliliter (ng/mL)
Standard Deviation 11.2
|
61.6 nanograms per milliliter (ng/mL)
Standard Deviation 25.5
|
57.5 nanograms per milliliter (ng/mL)
Standard Deviation 17.9
|
49.9 nanograms per milliliter (ng/mL)
Standard Deviation 37.0
|
120 nanograms per milliliter (ng/mL)
Standard Deviation 22.0
|
121 nanograms per milliliter (ng/mL)
Standard Deviation 32.2
|
86.3 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 2 hours
|
0.965 nanograms per milliliter (ng/mL)
Standard Deviation 0.0894
|
3.83 nanograms per milliliter (ng/mL)
Standard Deviation 1.01
|
12.3 nanograms per milliliter (ng/mL)
Standard Deviation 2.80
|
44.0 nanograms per milliliter (ng/mL)
Standard Deviation 18.5
|
83.0 nanograms per milliliter (ng/mL)
Standard Deviation 19.6
|
98.9 nanograms per milliliter (ng/mL)
Standard Deviation 21.8
|
100 nanograms per milliliter (ng/mL)
Standard Deviation 27.1
|
77.4 nanograms per milliliter (ng/mL)
Standard Deviation 21.5
|
97.6 nanograms per milliliter (ng/mL)
Standard Deviation 21.7
|
14.0 nanograms per milliliter (ng/mL)
Standard Deviation 2.74
|
38.7 nanograms per milliliter (ng/mL)
Standard Deviation 17.4
|
42.5 nanograms per milliliter (ng/mL)
Standard Deviation 9.20
|
43.6 nanograms per milliliter (ng/mL)
Standard Deviation 11.5
|
42.6 nanograms per milliliter (ng/mL)
Standard Deviation 13.8
|
34.0 nanograms per milliliter (ng/mL)
Standard Deviation 18.8
|
94.9 nanograms per milliliter (ng/mL)
Standard Deviation 19.7
|
93.5 nanograms per milliliter (ng/mL)
Standard Deviation 30.7
|
70.7 nanograms per milliliter (ng/mL)
Standard Deviation 5.51
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 4 hours
|
0.142 nanograms per milliliter (ng/mL)
Standard Deviation 0.318
|
1.87 nanograms per milliliter (ng/mL)
Standard Deviation 0.710
|
6.97 nanograms per milliliter (ng/mL)
Standard Deviation 2.25
|
25.2 nanograms per milliliter (ng/mL)
Standard Deviation 11.7
|
51.4 nanograms per milliliter (ng/mL)
Standard Deviation 15.9
|
57.4 nanograms per milliliter (ng/mL)
Standard Deviation 11.9
|
62.1 nanograms per milliliter (ng/mL)
Standard Deviation 26.5
|
50.1 nanograms per milliliter (ng/mL)
Standard Deviation 16.2
|
66.4 nanograms per milliliter (ng/mL)
Standard Deviation 15.9
|
8.74 nanograms per milliliter (ng/mL)
Standard Deviation 1.50
|
21.9 nanograms per milliliter (ng/mL)
Standard Deviation 7.94
|
25.6 nanograms per milliliter (ng/mL)
Standard Deviation 5.22
|
27.6 nanograms per milliliter (ng/mL)
Standard Deviation 7.91
|
26.4 nanograms per milliliter (ng/mL)
Standard Deviation 8.67
|
22.5 nanograms per milliliter (ng/mL)
Standard Deviation 13.6
|
63.8 nanograms per milliliter (ng/mL)
Standard Deviation 12.3
|
59.7 nanograms per milliliter (ng/mL)
Standard Deviation 15.5
|
48.9 nanograms per milliliter (ng/mL)
Standard Deviation 12.6
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 8 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.453 nanograms per milliliter (ng/mL)
Standard Deviation 0.314
|
2.55 nanograms per milliliter (ng/mL)
Standard Deviation 1.27
|
10.0 nanograms per milliliter (ng/mL)
Standard Deviation 4.85
|
21.6 nanograms per milliliter (ng/mL)
Standard Deviation 7.61
|
24.9 nanograms per milliliter (ng/mL)
Standard Deviation 9.77
|
31.2 nanograms per milliliter (ng/mL)
Standard Deviation 16.9
|
31.8 nanograms per milliliter (ng/mL)
Standard Deviation 28.9
|
32.5 nanograms per milliliter (ng/mL)
Standard Deviation 7.83
|
4.49 nanograms per milliliter (ng/mL)
Standard Deviation 1.26
|
9.63 nanograms per milliliter (ng/mL)
Standard Deviation 4.37
|
10.2 nanograms per milliliter (ng/mL)
Standard Deviation 2.88
|
10.8 nanograms per milliliter (ng/mL)
Standard Deviation 4.41
|
10.8 nanograms per milliliter (ng/mL)
Standard Deviation 4.29
|
11.8 nanograms per milliliter (ng/mL)
Standard Deviation 11.9
|
27.7 nanograms per milliliter (ng/mL)
Standard Deviation 6.94
|
30.2 nanograms per milliliter (ng/mL)
Standard Deviation 8.92
|
18.7 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 16 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.522 nanograms per milliliter (ng/mL)
Standard Deviation 0.641
|
1.50 nanograms per milliliter (ng/mL)
Standard Deviation 1.20
|
7.27 nanograms per milliliter (ng/mL)
Standard Deviation 4.49
|
—
|
—
|
—
|
—
|
—
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
—
|
—
|
4.95 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
—
|
—
|
—
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 1: 24 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.106 nanograms per milliliter (ng/mL)
Standard Deviation 0.280
|
1.19 nanograms per milliliter (ng/mL)
Standard Deviation 0.633
|
2.95 nanograms per milliliter (ng/mL)
Standard Deviation 1.61
|
3.21 nanograms per milliliter (ng/mL)
Standard Deviation 0.253
|
5.18 nanograms per milliliter (ng/mL)
Standard Deviation 4.20
|
3.64 nanograms per milliliter (ng/mL)
Standard Deviation 1.90
|
3.53 nanograms per milliliter (ng/mL)
Standard Deviation 1.25
|
0.498 nanograms per milliliter (ng/mL)
Standard Deviation 0.704
|
1.46 nanograms per milliliter (ng/mL)
Standard Deviation 0.803
|
1.64 nanograms per milliliter (ng/mL)
Standard Deviation 1.44
|
1.64 nanograms per milliliter (ng/mL)
Standard Deviation 1.42
|
1.29 nanograms per milliliter (ng/mL)
Standard Deviation 0.749
|
2.94 nanograms per milliliter (ng/mL)
Standard Deviation 6.88
|
4.49 nanograms per milliliter (ng/mL)
Standard Deviation 2.06
|
13.8 nanograms per milliliter (ng/mL)
Standard Deviation 43.0
|
3.45 nanograms per milliliter (ng/mL)
Standard Deviation 1.59
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 0.5 hour
|
2.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.238
|
6.00 nanograms per milliliter (ng/mL)
Standard Deviation 1.45
|
20.1 nanograms per milliliter (ng/mL)
Standard Deviation 8.08
|
71.3 nanograms per milliliter (ng/mL)
Standard Deviation 14.0
|
111 nanograms per milliliter (ng/mL)
Standard Deviation 26.0
|
112 nanograms per milliliter (ng/mL)
Standard Deviation 14.6
|
104 nanograms per milliliter (ng/mL)
Standard Deviation 13.0
|
85.1 nanograms per milliliter (ng/mL)
Standard Deviation 28.1
|
101 nanograms per milliliter (ng/mL)
Standard Deviation 29.2
|
19.5 nanograms per milliliter (ng/mL)
Standard Deviation 3.90
|
49.5 nanograms per milliliter (ng/mL)
Standard Deviation 19.7
|
58.3 nanograms per milliliter (ng/mL)
Standard Deviation 25.3
|
63.6 nanograms per milliliter (ng/mL)
Standard Deviation 41.8
|
61.1 nanograms per milliliter (ng/mL)
Standard Deviation 30.1
|
51.8 nanograms per milliliter (ng/mL)
Standard Deviation 29.6
|
118 nanograms per milliliter (ng/mL)
Standard Deviation 2.15
|
111 nanograms per milliliter (ng/mL)
Standard Deviation 42.4
|
104 nanograms per milliliter (ng/mL)
Standard Deviation 1.86
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 1 hour
|
1.55 nanograms per milliliter (ng/mL)
Standard Deviation 0.245
|
5.28 nanograms per milliliter (ng/mL)
Standard Deviation 1.07
|
13.8 nanograms per milliliter (ng/mL)
Standard Deviation 7.79
|
48.9 nanograms per milliliter (ng/mL)
Standard Deviation 26.6
|
87.6 nanograms per milliliter (ng/mL)
Standard Deviation 14.7
|
98.4 nanograms per milliliter (ng/mL)
Standard Deviation 10.5
|
70.3 nanograms per milliliter (ng/mL)
Standard Deviation 9.27
|
78.0 nanograms per milliliter (ng/mL)
Standard Deviation 29.5
|
83.8 nanograms per milliliter (ng/mL)
Standard Deviation 14.8
|
18.9 nanograms per milliliter (ng/mL)
Standard Deviation 2.50
|
45.6 nanograms per milliliter (ng/mL)
Standard Deviation 22.3
|
47.2 nanograms per milliliter (ng/mL)
Standard Deviation 12.7
|
47.3 nanograms per milliliter (ng/mL)
Standard Deviation 12.2
|
41.9 nanograms per milliliter (ng/mL)
Standard Deviation 11.7
|
45.0 nanograms per milliliter (ng/mL)
Standard Deviation 28.2
|
105 nanograms per milliliter (ng/mL)
Standard Deviation 14.3
|
102 nanograms per milliliter (ng/mL)
Standard Deviation 29.5
|
89.8 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 2 hours
|
0.909 nanograms per milliliter (ng/mL)
Standard Deviation 0.164
|
3.53 nanograms per milliliter (ng/mL)
Standard Deviation 1.10
|
9.26 nanograms per milliliter (ng/mL)
Standard Deviation 5.76
|
30.1 nanograms per milliliter (ng/mL)
Standard Deviation 18.1
|
65.2 nanograms per milliliter (ng/mL)
Standard Deviation 22.1
|
66.4 nanograms per milliliter (ng/mL)
Standard Deviation 6.97
|
66.2 nanograms per milliliter (ng/mL)
Standard Deviation 15.1
|
57.8 nanograms per milliliter (ng/mL)
Standard Deviation 20.2
|
61.0 nanograms per milliliter (ng/mL)
Standard Deviation 14.3
|
13.1 nanograms per milliliter (ng/mL)
Standard Deviation 0.626
|
31.8 nanograms per milliliter (ng/mL)
Standard Deviation 17.0
|
30.6 nanograms per milliliter (ng/mL)
Standard Deviation 9.57
|
31.8 nanograms per milliliter (ng/mL)
Standard Deviation 9.39
|
27.4 nanograms per milliliter (ng/mL)
Standard Deviation 9.80
|
39.6 nanograms per milliliter (ng/mL)
Standard Deviation 38.3
|
65.1 nanograms per milliliter (ng/mL)
Standard Deviation 0.651
|
71.1 nanograms per milliliter (ng/mL)
Standard Deviation 23.8
|
66.5 nanograms per milliliter (ng/mL)
Standard Deviation 4.01
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 4 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
1.17 nanograms per milliliter (ng/mL)
Standard Deviation 0.450
|
4.17 nanograms per milliliter (ng/mL)
Standard Deviation 3.72
|
12.9 nanograms per milliliter (ng/mL)
Standard Deviation 7.19
|
32.0 nanograms per milliliter (ng/mL)
Standard Deviation 14.0
|
29.1 nanograms per milliliter (ng/mL)
Standard Deviation 7.92
|
28.0 nanograms per milliliter (ng/mL)
Standard Deviation 14.0
|
39.4 nanograms per milliliter (ng/mL)
Standard Deviation 43.2
|
30.3 nanograms per milliliter (ng/mL)
Standard Deviation 6.20
|
6.18 nanograms per milliliter (ng/mL)
Standard Deviation 0.687
|
13.1 nanograms per milliliter (ng/mL)
Standard Deviation 11.7
|
13.2 nanograms per milliliter (ng/mL)
Standard Deviation 5.51
|
17.2 nanograms per milliliter (ng/mL)
Standard Deviation 18.5
|
13.0 nanograms per milliliter (ng/mL)
Standard Deviation 7.01
|
17.7 nanograms per milliliter (ng/mL)
Standard Deviation 16.2
|
28.4 nanograms per milliliter (ng/mL)
Standard Deviation 1.42
|
32.4 nanograms per milliliter (ng/mL)
Standard Deviation 13.5
|
33.4 nanograms per milliliter (ng/mL)
Standard Deviation 7.99
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 8 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
1.16 nanograms per milliliter (ng/mL)
Standard Deviation 1.31
|
3.25 nanograms per milliliter (ng/mL)
Standard Deviation 1.84
|
6.67 nanograms per milliliter (ng/mL)
Standard Deviation 2.74
|
6.68 nanograms per milliliter (ng/mL)
Standard Deviation 1.85
|
5.06 nanograms per milliliter (ng/mL)
Standard Deviation 1.68
|
6.78 nanograms per milliliter (ng/mL)
Standard Deviation 3.25
|
6.33 nanograms per milliliter (ng/mL)
Standard Deviation 2.04
|
1.86 nanograms per milliliter (ng/mL)
Standard Deviation 0.257
|
3.39 nanograms per milliliter (ng/mL)
Standard Deviation 3.39
|
3.41 nanograms per milliliter (ng/mL)
Standard Deviation 1.66
|
4.85 nanograms per milliliter (ng/mL)
Standard Deviation 3.63
|
3.26 nanograms per milliliter (ng/mL)
Standard Deviation 1.32
|
7.80 nanograms per milliliter (ng/mL)
Standard Deviation 12.3
|
20.2 nanograms per milliliter (ng/mL)
Standard Deviation 18.7
|
8.60 nanograms per milliliter (ng/mL)
Standard Deviation 5.71
|
7.22 nanograms per milliliter (ng/mL)
Standard Deviation 0.698
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 16 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.158 nanograms per milliliter (ng/mL)
Standard Deviation 0.316
|
0.244 nanograms per milliliter (ng/mL)
Standard Deviation 0.488
|
0.625 nanograms per milliliter (ng/mL)
Standard Deviation 0.586
|
1.65 nanograms per milliliter (ng/mL)
Standard Deviation 0.707
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 24 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.147 nanograms per milliliter (ng/mL)
Standard Deviation 0.294
|
0.221 nanograms per milliliter (ng/mL)
Standard Deviation 0.382
|
1.38 nanograms per milliliter (ng/mL)
Standard Deviation 0.631
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 72 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.498 nanograms per milliliter (ng/mL)
Standard Deviation 0.596
|
0.824 nanograms per milliliter (ng/mL)
Standard Deviation 0.333
|
0.664 nanograms per milliliter (ng/mL)
Standard Deviation 0.597
|
0.623 nanograms per milliliter (ng/mL)
Standard Deviation 0.973
|
0.538 nanograms per milliliter (ng/mL)
Standard Deviation 0.383
|
—
|
—
|
—
|
0.210 nanograms per milliliter (ng/mL)
Standard Deviation 0.419
|
0.103 nanograms per milliliter (ng/mL)
Standard Deviation 0.273
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
—
|
0.610 nanograms per milliliter (ng/mL)
Standard Deviation 0.00778
|
0.989 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 0 hour
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
8.24 nanograms per milliliter (ng/mL)
Standard Deviation 24.7
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
2.11 nanograms per milliliter (ng/mL)
Standard Deviation 13.7
|
0.120 nanograms per milliliter (ng/mL)
Standard Deviation 0.410
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.0170 nanograms per milliliter (ng/mL)
Standard Deviation 0.0945
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
2.10 nanograms per milliliter (ng/mL)
Standard Deviation 9.24
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.372 nanograms per milliliter (ng/mL)
Standard Deviation 1.36
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 0.5 hour
|
1.80 nanograms per milliliter (ng/mL)
Standard Deviation 0.590
|
5.42 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
20.7 nanograms per milliliter (ng/mL)
Standard Deviation 6.83
|
72.2 nanograms per milliliter (ng/mL)
Standard Deviation 13.0
|
105 nanograms per milliliter (ng/mL)
Standard Deviation 23.9
|
113 nanograms per milliliter (ng/mL)
Standard Deviation 15.1
|
121 nanograms per milliliter (ng/mL)
Standard Deviation 40.4
|
174 nanograms per milliliter (ng/mL)
Standard Deviation 372
|
123 nanograms per milliliter (ng/mL)
Standard Deviation 31.7
|
15.8 nanograms per milliliter (ng/mL)
Standard Deviation 2.82
|
56.3 nanograms per milliliter (ng/mL)
Standard Deviation 9.99
|
57.8 nanograms per milliliter (ng/mL)
Standard Deviation 15.4
|
79.6 nanograms per milliliter (ng/mL)
Standard Deviation 93.1
|
55.7 nanograms per milliliter (ng/mL)
Standard Deviation 22.7
|
51.1 nanograms per milliliter (ng/mL)
Standard Deviation 28.0
|
113 nanograms per milliliter (ng/mL)
Standard Deviation 16.8
|
137 nanograms per milliliter (ng/mL)
Standard Deviation 47.3
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 4 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
1.31 nanograms per milliliter (ng/mL)
Standard Deviation 0.422
|
7.16 nanograms per milliliter (ng/mL)
Standard Deviation 3.53
|
27.8 nanograms per milliliter (ng/mL)
Standard Deviation 10.6
|
45.1 nanograms per milliliter (ng/mL)
Standard Deviation 14.0
|
50.5 nanograms per milliliter (ng/mL)
Standard Deviation 16.2
|
52.5 nanograms per milliliter (ng/mL)
Standard Deviation 15.8
|
46.8 nanograms per milliliter (ng/mL)
Standard Deviation 16.5
|
57.1 nanograms per milliliter (ng/mL)
Standard Deviation 14.9
|
7.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.412
|
19.5 nanograms per milliliter (ng/mL)
Standard Deviation 4.90
|
25.1 nanograms per milliliter (ng/mL)
Standard Deviation 12.7
|
24.0 nanograms per milliliter (ng/mL)
Standard Deviation 7.15
|
21.4 nanograms per milliliter (ng/mL)
Standard Deviation 8.75
|
24.1 nanograms per milliliter (ng/mL)
Standard Deviation 19.1
|
54.9 nanograms per milliliter (ng/mL)
Standard Deviation 6.38
|
54.7 nanograms per milliliter (ng/mL)
Standard Deviation 16.7
|
58.0 nanograms per milliliter (ng/mL)
Standard Deviation 8.50
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 0 hour
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.0868 nanograms per milliliter (ng/mL)
Standard Deviation 0.213
|
0.914 nanograms per milliliter (ng/mL)
Standard Deviation 0.614
|
1.36 nanograms per milliliter (ng/mL)
Standard Deviation 0.589
|
2.24 nanograms per milliliter (ng/mL)
Standard Deviation 1.46
|
2.36 nanograms per milliliter (ng/mL)
Standard Deviation 1.11
|
1.58 nanograms per milliliter (ng/mL)
Standard Deviation 0.653
|
1.72 nanograms per milliliter (ng/mL)
Standard Deviation 0.599
|
0.180 nanograms per milliliter (ng/mL)
Standard Deviation 0.312
|
0.756 nanograms per milliliter (ng/mL)
Standard Deviation 0.786
|
2.14 nanograms per milliliter (ng/mL)
Standard Deviation 6.54
|
0.922 nanograms per milliliter (ng/mL)
Standard Deviation 0.670
|
1.01 nanograms per milliliter (ng/mL)
Standard Deviation 1.71
|
4.17 nanograms per milliliter (ng/mL)
Standard Deviation 8.72
|
1.45 nanograms per milliliter (ng/mL)
Standard Deviation 0.417
|
2.17 nanograms per milliliter (ng/mL)
Standard Deviation 1.46
|
1.86 nanograms per milliliter (ng/mL)
Standard Deviation 0.354
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 2 hours
|
0.988 nanograms per milliliter (ng/mL)
Standard Deviation 0.0219
|
2.84 nanograms per milliliter (ng/mL)
Standard Deviation 0.751
|
9.09 nanograms per milliliter (ng/mL)
Standard Deviation 3.13
|
29.9 nanograms per milliliter (ng/mL)
Standard Deviation 12.3
|
58.4 nanograms per milliliter (ng/mL)
Standard Deviation 19.3
|
59.0 nanograms per milliliter (ng/mL)
Standard Deviation 6.87
|
49.9 nanograms per milliliter (ng/mL)
Standard Deviation 15.2
|
55.3 nanograms per milliliter (ng/mL)
Standard Deviation 20.9
|
62.0 nanograms per milliliter (ng/mL)
Standard Deviation 17.8
|
10.3 nanograms per milliliter (ng/mL)
Standard Deviation 4.44
|
21.3 nanograms per milliliter (ng/mL)
Standard Deviation 4.81
|
28.6 nanograms per milliliter (ng/mL)
Standard Deviation 9.10
|
29.9 nanograms per milliliter (ng/mL)
Standard Deviation 9.94
|
28.5 nanograms per milliliter (ng/mL)
Standard Deviation 9.68
|
36.7 nanograms per milliliter (ng/mL)
Standard Deviation 27.9
|
57.6 nanograms per milliliter (ng/mL)
Standard Deviation 10.5
|
59.9 nanograms per milliliter (ng/mL)
Standard Deviation 19.7
|
67.3 nanograms per milliliter (ng/mL)
Standard Deviation 4.50
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 8 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
2.32 nanograms per milliliter (ng/mL)
Standard Deviation 1.45
|
9.29 nanograms per milliliter (ng/mL)
Standard Deviation 4.62
|
16.5 nanograms per milliliter (ng/mL)
Standard Deviation 7.44
|
18.7 nanograms per milliliter (ng/mL)
Standard Deviation 9.48
|
24.9 nanograms per milliliter (ng/mL)
Standard Deviation 13.1
|
26.8 nanograms per milliliter (ng/mL)
Standard Deviation 35.4
|
24.1 nanograms per milliliter (ng/mL)
Standard Deviation 8.09
|
2.51 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
8.66 nanograms per milliliter (ng/mL)
Standard Deviation 4.83
|
7.91 nanograms per milliliter (ng/mL)
Standard Deviation 3.47
|
8.85 nanograms per milliliter (ng/mL)
Standard Deviation 3.92
|
7.40 nanograms per milliliter (ng/mL)
Standard Deviation 3.67
|
12.8 nanograms per milliliter (ng/mL)
Standard Deviation 18.3
|
24.3 nanograms per milliliter (ng/mL)
Standard Deviation 3.79
|
24.0 nanograms per milliliter (ng/mL)
Standard Deviation 11.5
|
26.4 nanograms per milliliter (ng/mL)
Standard Deviation 6.55
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 16 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.405 nanograms per milliliter (ng/mL)
Standard Deviation 0.701
|
2.47 nanograms per milliliter (ng/mL)
Standard Deviation 2.14
|
4.24 nanograms per milliliter (ng/mL)
Standard Deviation 3.60
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
1.97 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
1.69 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
—
|
—
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 1: 24 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.205 nanograms per milliliter (ng/mL)
Standard Deviation 0.410
|
0.219 nanograms per milliliter (ng/mL)
Standard Deviation 0.342
|
0.940 nanograms per milliliter (ng/mL)
Standard Deviation 0.561
|
2.11 nanograms per milliliter (ng/mL)
Standard Deviation 1.45
|
1.81 nanograms per milliliter (ng/mL)
Standard Deviation 1.30
|
2.51 nanograms per milliliter (ng/mL)
Standard Deviation 1.19
|
2.03 nanograms per milliliter (ng/mL)
Standard Deviation 1.69
|
1.95 nanograms per milliliter (ng/mL)
Standard Deviation 0.854
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.737 nanograms per milliliter (ng/mL)
Standard Deviation 0.518
|
1.06 nanograms per milliliter (ng/mL)
Standard Deviation 1.06
|
1.16 nanograms per milliliter (ng/mL)
Standard Deviation 0.777
|
1.15 nanograms per milliliter (ng/mL)
Standard Deviation 1.40
|
4.96 nanograms per milliliter (ng/mL)
Standard Deviation 11.7
|
3.16 nanograms per milliliter (ng/mL)
Standard Deviation 1.58
|
2.98 nanograms per milliliter (ng/mL)
Standard Deviation 1.51
|
3.19 nanograms per milliliter (ng/mL)
Standard Deviation 1.10
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 0.5 hour
|
1.92 nanograms per milliliter (ng/mL)
Standard Deviation 0.296
|
6.06 nanograms per milliliter (ng/mL)
Standard Deviation 0.454
|
17.2 nanograms per milliliter (ng/mL)
Standard Deviation 3.44
|
69.1 nanograms per milliliter (ng/mL)
Standard Deviation 16.8
|
93.9 nanograms per milliliter (ng/mL)
Standard Deviation 22.2
|
98.8 nanograms per milliliter (ng/mL)
Standard Deviation 34.7
|
91.2 nanograms per milliliter (ng/mL)
Standard Deviation 40.2
|
153 nanograms per milliliter (ng/mL)
Standard Deviation 300
|
101 nanograms per milliliter (ng/mL)
Standard Deviation 18.6
|
13.4 nanograms per milliliter (ng/mL)
Standard Deviation 3.07
|
44.3 nanograms per milliliter (ng/mL)
Standard Deviation 9.53
|
64.2 nanograms per milliliter (ng/mL)
Standard Deviation 60.1
|
58.8 nanograms per milliliter (ng/mL)
Standard Deviation 38.5
|
52.7 nanograms per milliliter (ng/mL)
Standard Deviation 14.4
|
56.7 nanograms per milliliter (ng/mL)
Standard Deviation 31.1
|
100 nanograms per milliliter (ng/mL)
Standard Deviation 20.0
|
100 nanograms per milliliter (ng/mL)
Standard Deviation 28.8
|
103 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 1 hour
|
1.44 nanograms per milliliter (ng/mL)
Standard Deviation 0.260
|
4.82 nanograms per milliliter (ng/mL)
Standard Deviation 0.794
|
14.7 nanograms per milliliter (ng/mL)
Standard Deviation 3.80
|
44.9 nanograms per milliliter (ng/mL)
Standard Deviation 18.3
|
84.8 nanograms per milliliter (ng/mL)
Standard Deviation 23.7
|
90.5 nanograms per milliliter (ng/mL)
Standard Deviation 16.3
|
78.4 nanograms per milliliter (ng/mL)
Standard Deviation 39.9
|
94.8 nanograms per milliliter (ng/mL)
Standard Deviation 104
|
83.4 nanograms per milliliter (ng/mL)
Standard Deviation 19.4
|
16.8 nanograms per milliliter (ng/mL)
Standard Deviation 5.53
|
33.8 nanograms per milliliter (ng/mL)
Standard Deviation 7.91
|
69.8 nanograms per milliliter (ng/mL)
Standard Deviation 124
|
42.7 nanograms per milliliter (ng/mL)
Standard Deviation 12.9
|
42.3 nanograms per milliliter (ng/mL)
Standard Deviation 15.5
|
48.1 nanograms per milliliter (ng/mL)
Standard Deviation 28.2
|
86.3 nanograms per milliliter (ng/mL)
Standard Deviation 15.0
|
90.9 nanograms per milliliter (ng/mL)
Standard Deviation 24.6
|
89.7 nanograms per milliliter (ng/mL)
Standard Deviation 4.66
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 4 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
1.13 nanograms per milliliter (ng/mL)
Standard Deviation 0.471
|
4.18 nanograms per milliliter (ng/mL)
Standard Deviation 1.98
|
14.9 nanograms per milliliter (ng/mL)
Standard Deviation 6.75
|
27.1 nanograms per milliliter (ng/mL)
Standard Deviation 10.4
|
24.2 nanograms per milliliter (ng/mL)
Standard Deviation 2.26
|
24.3 nanograms per milliliter (ng/mL)
Standard Deviation 11.6
|
27.6 nanograms per milliliter (ng/mL)
Standard Deviation 8.71
|
29.1 nanograms per milliliter (ng/mL)
Standard Deviation 10.4
|
6.40 nanograms per milliliter (ng/mL)
Standard Deviation 2.13
|
8.11 nanograms per milliliter (ng/mL)
Standard Deviation 2.77
|
12.0 nanograms per milliliter (ng/mL)
Standard Deviation 4.47
|
14.8 nanograms per milliliter (ng/mL)
Standard Deviation 6.00
|
13.3 nanograms per milliliter (ng/mL)
Standard Deviation 5.22
|
25.2 nanograms per milliliter (ng/mL)
Standard Deviation 32.6
|
29.8 nanograms per milliliter (ng/mL)
Standard Deviation 2.81
|
30.8 nanograms per milliliter (ng/mL)
Standard Deviation 12.5
|
34.7 nanograms per milliliter (ng/mL)
Standard Deviation 8.12
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 16 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.218 nanograms per milliliter (ng/mL)
Standard Deviation 0.378
|
1.15 nanograms per milliliter (ng/mL)
Standard Deviation 0.687
|
1.64 nanograms per milliliter (ng/mL)
Standard Deviation 0.597
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 24 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.631 nanograms per milliliter (ng/mL)
Standard Deviation 0.630
|
1.38 nanograms per milliliter (ng/mL)
Standard Deviation 0.697
|
—
|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 72 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.200 nanograms per milliliter (ng/mL)
Standard Deviation 0.347
|
0.488 nanograms per milliliter (ng/mL)
Standard Deviation 0.376
|
0.611 nanograms per milliliter (ng/mL)
Standard Deviation 0.625
|
1.57 nanograms per milliliter (ng/mL)
Standard Deviation 0.584
|
0.578 nanograms per milliliter (ng/mL)
Standard Deviation 0.475
|
0.396 nanograms per milliliter (ng/mL)
Standard Deviation 0.450
|
—
|
—
|
—
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
—
|
1.17 nanograms per milliliter (ng/mL)
Standard Deviation 0.409
|
0.741 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 2 Day 5: 240 hours
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
—
|
—
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
—
|
|
Parts A, B, and C: Serum Concentrations of Nemvaleukin Alfa
Cycle 1 Day 5: 0 hour
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.00 nanograms per milliliter (ng/mL)
Standard Deviation 0.00
|
0.104 nanograms per milliliter (ng/mL)
Standard Deviation 0.276
|
0.619 nanograms per milliliter (ng/mL)
Standard Deviation 0.462
|
2.36 nanograms per milliliter (ng/mL)
Standard Deviation 2.29
|
1.59 nanograms per milliliter (ng/mL)
Standard Deviation 0.692
|
1.67 nanograms per milliliter (ng/mL)
Standard Deviation 0.531
|
1.51 nanograms per milliliter (ng/mL)
Standard Deviation 0.654
|
1.96 nanograms per milliliter (ng/mL)
Standard Deviation 0.987
|
0.209 nanograms per milliliter (ng/mL)
Standard Deviation 0.361
|
0.416 nanograms per milliliter (ng/mL)
Standard Deviation 0.538
|
1.10 nanograms per milliliter (ng/mL)
Standard Deviation 0.965
|
2.16 nanograms per milliliter (ng/mL)
Standard Deviation 3.95
|
0.933 nanograms per milliliter (ng/mL)
Standard Deviation 0.529
|
3.90 nanograms per milliliter (ng/mL)
Standard Deviation 9.89
|
2.03 nanograms per milliliter (ng/mL)
Standard Deviation 0.979
|
2.67 nanograms per milliliter (ng/mL)
Standard Deviation 2.06
|
1.92 nanograms per milliliter (ng/mL)
Standard Deviation 0.336
|
SECONDARY outcome
Timeframe: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dosePopulation: The PK population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=44 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=34 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=24 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=36 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=20 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
Cycle 2 Day 5
|
2.61 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 16.6
|
11.5 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.4
|
40.8 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 21.2
|
167 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 51.5
|
361 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 50.4
|
439 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 3.5
|
312 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 131.0
|
287 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 60.9
|
329 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 45.3
|
52.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.5
|
120 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 72.3
|
135 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 54.3
|
134 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 35.4
|
128 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 36.6
|
153 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 73.4
|
275 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 15.0
|
346 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 43.9
|
413 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 57.6
|
|
Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
Cycle 1 Day 1
|
2.96 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 53.1
|
17.0 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 35.6
|
66.5 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 36.5
|
195 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 252.1
|
557 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 28.7
|
616 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 42.3
|
719 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.7
|
608 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 30.1
|
723 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 23.2
|
84.1 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.5
|
248 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 23.4
|
286 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 22.1
|
296 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 35.0
|
276 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 31.4
|
222 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 77.2
|
698 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 21.7
|
715 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 37.6
|
543 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 25.0
|
|
Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
Cycle 1 Day 5
|
2.52 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 17.3
|
14.4 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 23.6
|
48.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 55.9
|
106 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 205.5
|
379 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 46.0
|
323 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 84.1
|
346 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 47.8
|
292 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 61.4
|
312 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 40.6
|
56.7 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 18.8
|
121 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 68.5
|
143 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 26.2
|
158 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 41.6
|
130 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 40.5
|
139 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 53.4
|
343 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 6.8
|
368 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 56.7
|
393 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 45.8
|
|
Parts A, B and C: Area Under Concentration From Time Zero to the Last Quantifiable Concentration (AUClast) of Nemvaleukin Alfa
Cycle 2 Day 1
|
2.47 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 32.4
|
15.3 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 45.4
|
69.2 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 50.3
|
274 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.0
|
478 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 30.7
|
512 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 35.6
|
573 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 36.8
|
517 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 44.5
|
594 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 25.9
|
56.1 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 12.9
|
195 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 50.1
|
235 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 30.8
|
243 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 41.5
|
212 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 39.6
|
224 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 85.0
|
625 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 12.5
|
562 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation 33.5
|
590 hour*nanogram per milliliter (h*ng/mL)
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation could not be calculated for 1 participant.
|
SECONDARY outcome
Timeframe: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dosePopulation: The PK population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=11 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=44 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=34 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=23 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=25 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=36 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=18 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
Cycle 1 Day 1
|
2.09 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 41.4
|
6.72 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 21.3
|
20.5 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 26.8
|
47.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 177.8
|
113 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 33.7
|
151 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 36.7
|
157 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 19.4
|
99.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 40.8
|
124 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 34.2
|
18.1 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 15.4
|
65.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 24.4
|
61.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 22.8
|
57.5 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 86.5
|
59.5 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 32.6
|
45.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 48.8
|
131 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 15.8
|
133 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 31.7
|
89.3 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 3.0
|
|
Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
Cycle 1 Day 5
|
1.99 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 10.3
|
6.36 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 24.5
|
37.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 19.2
|
41.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 178.7
|
108 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 22.5
|
112 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 13.5
|
104 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 12.5
|
82.1 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 32.3
|
95.1 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 33.8
|
19.2 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 21.7
|
46.5 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 41.6
|
55.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 37.5
|
53.1 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 57.9
|
54.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 51.8
|
47.0 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 40.1
|
118 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 1.8
|
101 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 51.5
|
104 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 1.8
|
|
Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
Cycle 2 Day 1
|
1.72 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 35.1
|
5.34 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 2.2
|
19.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 32.3
|
65.3 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 27.5
|
113 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 24.7
|
112 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 13.0
|
116 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 33.1
|
108 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 86.7
|
119 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 27.6
|
15.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 18.1
|
52.9 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 21.9
|
55.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 26.9
|
58.1 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 81.2
|
55.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 31.4
|
47.2 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 47.7
|
112 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 15.3
|
128 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 30.6
|
124 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation NA
Geometric Coefficient of Variation could not be calculated for 1 participant.
|
|
Parts A, B and C: Maximum Observed Serum Concentration (Cmax) of Nemvaleukin Alfa
Cycle 2 Day 5
|
1.90 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 11.0
|
6.39 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 12.7
|
16.7 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 18.5
|
52.9 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 48.1
|
97.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 29.0
|
95.7 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 37.0
|
83.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 57.4
|
103 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 69.5
|
99.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 18.3
|
14.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 24.0
|
40.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 26.9
|
50.3 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 67.9
|
51.7 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 52.0
|
51.0 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 25.9
|
49.8 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 52.6
|
99.2 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 20.3
|
96.6 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 29.7
|
94.4 nanograms per milliliters (ng/mL)
Geometric Coefficient of Variation 12.5
|
SECONDARY outcome
Timeframe: Cycle 1 and 2 Day 1: 0, 0.5, 1, 2, 4, 8, 16, and 24 hours post-dose; Cycle 1 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, and 72 hours post-dose; Cycle 2 Day 5: 0, 0.5, 1, 2, 4, 8, 16, 24, 72, and 240 hours post-dosePopulation: The PK population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least 1 measurable serum concentration of nemvaleukin alfa at any scheduled PK time point. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=11 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=44 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=34 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=23 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=25 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=36 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=18 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
Cycle 1 Day 1
|
0.60 hours
Interval 0.57 to 0.83
|
0.63 hours
Interval 0.52 to 0.73
|
0.55 hours
Interval 0.5 to 0.78
|
0.57 hours
Interval 0.5 to 0.75
|
0.57 hours
Interval 0.5 to 0.7
|
0.57 hours
Interval 0.53 to 0.57
|
0.51 hours
Interval 0.5 to 0.62
|
0.52 hours
Interval 0.5 to 0.75
|
0.50 hours
Interval 0.5 to 0.67
|
0.75 hours
Interval 0.57 to 0.98
|
0.73 hours
Interval 0.58 to 0.75
|
0.55 hours
Interval 0.48 to 1.0
|
0.55 hours
Interval 0.5 to 0.73
|
0.52 hours
Interval 0.4 to 0.63
|
0.50 hours
Interval 0.5 to 0.82
|
0.50 hours
Interval 0.5 to 0.67
|
0.53 hours
Interval 0.45 to 1.0
|
0.78 hours
Interval 0.5 to 1.07
|
|
Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
Cycle 1 Day 5
|
0.70 hours
Interval 0.5 to 0.8
|
0.60 hours
Interval 0.48 to 0.82
|
0.54 hours
Interval 0.5 to 0.8
|
0.55 hours
Interval 0.5 to 0.67
|
0.58 hours
Interval 0.53 to 0.73
|
0.53 hours
Interval 0.53 to 0.58
|
0.53 hours
Interval 0.5 to 0.68
|
0.51 hours
Interval 0.5 to 0.8
|
0.50 hours
Interval 0.43 to 0.58
|
0.58 hours
Interval 0.55 to 0.72
|
0.73 hours
Interval 0.55 to 0.77
|
0.57 hours
Interval 0.5 to 1.0
|
0.53 hours
Interval 0.3 to 0.85
|
0.55 hours
Interval 0.48 to 0.68
|
0.50 hours
Interval 0.5 to 0.75
|
0.58 hours
Interval 0.58 to 0.58
|
0.52 hours
Interval 0.45 to 0.63
|
0.83 hours
Interval 0.57 to 1.08
|
|
Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
Cycle 2 Day 1
|
0.67 hours
Interval 0.58 to 0.8
|
0.73 hours
Interval 0.72 to 0.75
|
0.53 hours
Interval 0.5 to 0.58
|
0.55 hours
Interval 0.5 to 0.87
|
0.58 hours
Interval 0.55 to 0.73
|
0.53 hours
Interval 0.52 to 0.58
|
0.52 hours
Interval 0.5 to 0.63
|
0.50 hours
Interval 0.5 to 0.77
|
0.50 hours
Interval 0.5 to 0.6
|
0.71 hours
Interval 0.6 to 0.82
|
0.68 hours
Interval 0.57 to 0.8
|
0.55 hours
Interval 0.5 to 1.0
|
0.53 hours
Interval 0.47 to 1.0
|
0.53 hours
Interval 0.5 to 0.58
|
0.50 hours
Interval 0.5 to 0.77
|
0.55 hours
Interval 0.5 to 0.58
|
0.52 hours
Interval 0.48 to 0.68
|
1.00 hours
Interval 1.0 to 1.0
|
|
Parts A, B and C: Time to Reach Cmax (Tmax) of Nemvaleukin Alfa
Cycle 2 Day 5
|
0.63 hours
Interval 0.55 to 0.8
|
0.57 hours
Interval 0.5 to 0.68
|
0.55 hours
Interval 0.5 to 0.75
|
0.68 hours
Interval 0.52 to 1.58
|
0.60 hours
Interval 0.5 to 0.75
|
0.58 hours
Interval 0.58 to 0.58
|
0.52 hours
Interval 0.5 to 0.52
|
0.50 hours
Interval 0.5 to 0.77
|
0.50 hours
Interval 0.5 to 0.67
|
0.72 hours
Interval 0.55 to 0.73
|
0.68 hours
Interval 0.58 to 0.78
|
0.55 hours
Interval 0.52 to 1.0
|
0.55 hours
Interval 0.5 to 1.08
|
0.50 hours
Interval 0.48 to 0.62
|
0.50 hours
Interval 0.5 to 0.62
|
0.56 hours
Interval 0.5 to 0.62
|
0.52 hours
Interval 0.5 to 0.58
|
0.77 hours
Interval 0.53 to 1.0
|
SECONDARY outcome
Timeframe: From first dose of study drug up to 9 months (for Part A); up to 40.3 months (for Part B); up to 50.5 months (for Part C)Population: Immunogenicity analysis set included all participants who received at least one dose of active study drug and had at least one post baseline blood sample collected to assess immunogenicity.
Overall proportion was calculated as: Number of participants (overall positive)/total number of participants in the cohort. Overall positive: Participants with at least 1 treatment-emergent ADA positive sample at any time during the treatment period.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=45 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=26 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=34 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=24 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=24 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=43 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=20 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B, and C: Proportion of Positive Anti-Nemvaleukin Alfa Antibodies (ADA)
|
0.00 proportion of participants
|
0.00 proportion of participants
|
0.143 proportion of participants
|
0.125 proportion of participants
|
0.417 proportion of participants
|
0.333 proportion of participants
|
0.600 proportion of participants
|
0.467 proportion of participants
|
0.500 proportion of participants
|
0.00 proportion of participants
|
0.667 proportion of participants
|
0.294 proportion of participants
|
0.250 proportion of participants
|
0.208 proportion of participants
|
0.581 proportion of participants
|
0.667 proportion of participants
|
0.200 proportion of participants
|
0.00 proportion of participants
|
SECONDARY outcome
Timeframe: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: No data collection or analysis based on immune-related response criteria (irRC) and iRECIST was performed as iRECIST was implemented during the middle of the study conduct to replace irRC. However, no data was collected and analyzed for iRECIST either. Therefore, no data is available to report for this outcome measure.
iORR was defined as the percentage of participants with objective evidence of immune CR (iCR) or immune PR (iPR) based on iRECIST guidelines.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: The antitumor evaluable population consisted of participants who complete 2 cycles of therapy and had at least one follow-up scan.
Disease control rate was defined as the percentage of participants with objective evidence of CR, PR, or SD based on RECIST v.1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=9 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=46 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=22 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=36 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=22 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=39 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=18 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B, and C: Disease Control Rate (DCR) Based on RECIST v.1.1
|
0.0 percentage of participants
Interval 0.0 to 60.2
|
25.0 percentage of participants
Interval 0.6 to 80.6
|
20.0 percentage of participants
Interval 0.5 to 71.6
|
60.0 percentage of participants
Interval 14.7 to 94.7
|
33.3 percentage of participants
Interval 7.5 to 70.1
|
33.3 percentage of participants
Interval 0.8 to 90.6
|
25.0 percentage of participants
Interval 0.6 to 80.6
|
47.8 percentage of participants
Interval 32.9 to 63.1
|
50.0 percentage of participants
Interval 28.2 to 71.8
|
0.0 percentage of participants
Interval 0.0 to 70.8
|
30.6 percentage of participants
Interval 16.3 to 48.1
|
22.7 percentage of participants
Interval 7.8 to 45.4
|
47.6 percentage of participants
Interval 25.7 to 70.2
|
46.2 percentage of participants
Interval 30.1 to 62.8
|
66.7 percentage of participants
Interval 9.4 to 99.2
|
50.0 percentage of participants
Interval 26.0 to 74.0
|
100 percentage of participants
Interval 15.8 to 100.0
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug up to 9 months for Part A; up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: No data collection or analysis based on irRC and iRECIST was performed as iRECIST was implemented during the middle of the study conduct to replace irRC. However, no data was collected and analyzed for iRECIST either. Therefore, no data is available to report for this outcome measure.
iDCR was defined as the percentage of participants with objective evidence of iCR, iPR (where iCR or iPR required confirmation), or immune stable disease (iSD) (where the iSD requires to occur at Cycle 4 or later).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause (up to 40.3 months for Part B and up to 50.5 months for Part C)Population: The antitumor evaluable population consisted of participants who complete 2 cycles of therapy and had at least one follow-up scan. Here, "overall number of participants analyzed" signified participants who had CR or PR.
Duration of response was defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=6 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=1 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=2 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=2 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=1 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts B, and C: Duration of Response (DOR) Based on RECIST v1.1
|
18.43 weeks
Interval 6.14 to
Here, NA means upper limit of confidence interval could not be estimated due to insufficient events.
|
28.86 weeks
Interval 12.43 to
Here, NA means upper limit of confidence interval could not be estimated due to insufficient events.
|
—
|
35.14 weeks
Interval 8.29 to 160.14
|
NA weeks
Here, NA means median and confidence interval could not be estimated due to insufficient events.
|
63.14 weeks
Interval 6.86 to
Here, NA means upper limit of confidence interval could not be estimated due to insufficient events.
|
NA weeks
Interval 7.14 to
Here, NA means median and upper limit of confidence interval could not be estimated due to insufficient events.
|
NA weeks
Here, NA means median and confidence interval could not be estimated due to insufficient events.
|
39.07 weeks
Interval 13.14 to 65.0
|
27.86 weeks
Here, NA means lower and upper limit of confidence interval could not be estimated due to insufficient events.
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: No data collection or analysis based on irRC and iRECIST was performed as iRECIST was implemented during the middle of the study conduct to replace irRC. However, no data was collected and analyzed for iRECIST either. Therefore, no data is available to report for this outcome measure.
iDOR was defined as the time from the first documentation of response (iCR or iPR) to the first documentation of objective tumor progression (immune confirmed progressive disease \[iCPD\]) or death due to any cause based on iRECIST.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: As pre-specified in statistical analysis plan, this outcome measure of DRR was not summarized and hence, no data was reported in this outcome measure.
DRR was defined as the percentage of participants with an objective response (complete or partial response per RECIST 1.1) lasting continuously for 6 months and starting any time within 12 months of initiating the study drug.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: No data collection or analysis based on irRC and iRECIST was performed as iRECIST was implemented during the middle of the study conduct to replace irRC. However, no data was collected and analyzed for iRECIST either. Therefore, no data is available to report for this outcome measure.
iDRR was defined as the percentage of participants with an objective response (complete or partial response per iRECIST) lasting continuously for 6 months and starting any time within 12 months of initiating the study drug.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: From first dose of study drug up to the first documentation of objective tumor progression or death due to any cause (up to 40.3 months for Part B and up to 50.5 months for Part C)Population: The antitumor evaluable population consisted of participants who complete 2 cycles of therapy and had at least one follow-up scan.
Progression-free survival was defined as the time from the first dose of nemvaleukin to the first documentation of objective tumor progression or death due to any cause. PD: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this included the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=46 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=22 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=18 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=2 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Part B and Part C Cohorts C5, C6, C7: Progression-free Survival (PFS) Based on RECIST v.1.1
|
16.14 weeks
Interval 10.57 to 17.14
|
12.43 weeks
Interval 4.43 to 22.57
|
NA weeks
Interval 10.29 to
Here, NA means median and upper limit of confidence interval could not be estimated due to insufficient events.
|
18.64 weeks
Interval 6.14 to 27.14
|
35.57 weeks
Interval 18.71 to 52.43
|
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|
—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
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—
|
SECONDARY outcome
Timeframe: From first dose of study drug up to 40.3 months for Part B; up to 50.5 months for Part CPopulation: No data collection or analysis based on irRC and iRECIST was performed as iRECIST was implemented during the middle of the study conduct to replace irRC. However, no data was collected and analyzed for iRECIST either. Therefore, no data is available to report for this outcome measure.
iPFS was defined as the time from the first dose of study medication to the first documentation of objective tumor progression based on iRECIST (immune confirmed progressive disease \[iCPD\]) or death due to any cause.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Cycle 1 Day 1 (Cycle 1 length = 14 days for Part A and 21 days for Part B and C)Population: The pharmacodynamic (PD) population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least one available postbaseline PD measurement. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=27 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=47 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=36 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=25 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=39 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B and C: Maximum Cell Count of Whole Blood FoxP3+ T Cells (Tregs), Total Cluster of Differentiation (CD)8+ T Cells and Natural Killer (NK) Cells
Whole Blood FoxP3+ T Cells (Tregs)
|
32.0 cells per microliters (cells/mcL)
Standard Deviation 11.3
|
50.5 cells per microliters (cells/mcL)
Standard Deviation 53.7
|
56.6 cells per microliters (cells/mcL)
Standard Deviation 22.3
|
46.3 cells per microliters (cells/mcL)
Standard Deviation 21.8
|
43.3 cells per microliters (cells/mcL)
Standard Deviation 28.2
|
57.4 cells per microliters (cells/mcL)
Standard Deviation 14.4
|
51.3 cells per microliters (cells/mcL)
Standard Deviation 36.0
|
40.3 cells per microliters (cells/mcL)
Standard Deviation 23.5
|
47.9 cells per microliters (cells/mcL)
Standard Deviation 24.0
|
27.4 cells per microliters (cells/mcL)
Standard Deviation 7.31
|
50.9 cells per microliters (cells/mcL)
Standard Deviation 23.9
|
42.6 cells per microliters (cells/mcL)
Standard Deviation 28.3
|
37.8 cells per microliters (cells/mcL)
Standard Deviation 24.5
|
41.6 cells per microliters (cells/mcL)
Standard Deviation 27.7
|
44.3 cells per microliters (cells/mcL)
Standard Deviation 22.5
|
51.1 cells per microliters (cells/mcL)
Standard Deviation 9.85
|
52.6 cells per microliters (cells/mcL)
Standard Deviation 31.3
|
33.1 cells per microliters (cells/mcL)
Standard Deviation NA
Standard Deviation could not be calculated for 1 participant.
|
|
Parts A, B and C: Maximum Cell Count of Whole Blood FoxP3+ T Cells (Tregs), Total Cluster of Differentiation (CD)8+ T Cells and Natural Killer (NK) Cells
Total CD8+ T Cells
|
247 cells per microliters (cells/mcL)
Standard Deviation 107
|
204 cells per microliters (cells/mcL)
Standard Deviation 89.2
|
262 cells per microliters (cells/mcL)
Standard Deviation 64.2
|
466 cells per microliters (cells/mcL)
Standard Deviation 255
|
610 cells per microliters (cells/mcL)
Standard Deviation 570
|
704 cells per microliters (cells/mcL)
Standard Deviation 559
|
703 cells per microliters (cells/mcL)
Standard Deviation 502
|
1392 cells per microliters (cells/mcL)
Standard Deviation 1053
|
773 cells per microliters (cells/mcL)
Standard Deviation 422
|
262 cells per microliters (cells/mcL)
Standard Deviation 186
|
551 cells per microliters (cells/mcL)
Standard Deviation 433
|
562 cells per microliters (cells/mcL)
Standard Deviation 373
|
533 cells per microliters (cells/mcL)
Standard Deviation 328
|
688 cells per microliters (cells/mcL)
Standard Deviation 384
|
718 cells per microliters (cells/mcL)
Standard Deviation 567
|
924 cells per microliters (cells/mcL)
Standard Deviation 638
|
762 cells per microliters (cells/mcL)
Standard Deviation 538
|
445 cells per microliters (cells/mcL)
Standard Deviation 349
|
|
Parts A, B and C: Maximum Cell Count of Whole Blood FoxP3+ T Cells (Tregs), Total Cluster of Differentiation (CD)8+ T Cells and Natural Killer (NK) Cells
NK Cells
|
197 cells per microliters (cells/mcL)
Standard Deviation 61.4
|
343 cells per microliters (cells/mcL)
Standard Deviation 20.6
|
467 cells per microliters (cells/mcL)
Standard Deviation 313
|
685 cells per microliters (cells/mcL)
Standard Deviation 307
|
1053 cells per microliters (cells/mcL)
Standard Deviation 660
|
978 cells per microliters (cells/mcL)
Standard Deviation 400
|
1038 cells per microliters (cells/mcL)
Standard Deviation 1028
|
1279 cells per microliters (cells/mcL)
Standard Deviation 642
|
1470 cells per microliters (cells/mcL)
Standard Deviation 873
|
531 cells per microliters (cells/mcL)
Standard Deviation 296
|
804 cells per microliters (cells/mcL)
Standard Deviation 196
|
771 cells per microliters (cells/mcL)
Standard Deviation 503
|
760 cells per microliters (cells/mcL)
Standard Deviation 458
|
813 cells per microliters (cells/mcL)
Standard Deviation 436
|
889 cells per microliters (cells/mcL)
Standard Deviation 438
|
1081 cells per microliters (cells/mcL)
Standard Deviation 787
|
1064 cells per microliters (cells/mcL)
Standard Deviation 445
|
1298 cells per microliters (cells/mcL)
Standard Deviation 334
|
SECONDARY outcome
Timeframe: Cycle 1 Days 1 and 5; Cycle 2 Days 1 and 5 (Cycle 1 length = 14 days for Part A and 21 days for Part B and C; Cycle 2 length= 21 days for all parts)Population: The PD population consisted of all participants who received at least 1 dose of nemvaleukin alfa and had at least one available postbaseline PD measurement. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and "number analyzed" signifies participants who were evaluable at specified timepoints.
Outcome measures
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 Participants
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 Participants
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=10 Participants
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=2 Participants
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 Participants
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=34 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=15 Participants
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 Participants
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg+Pembrolizumab 200 mg
n=6 Participants
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=31 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=17 Participants
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=20 Participants
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 Participants
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=18 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin 6 Alfa mcg/kg + Pembrolizumab 200 mg
n=2 Participants
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
INF-γ: Cycle 1 Day 1
|
23.0 nanogram per liter (ng/L)
Standard Deviation 10.3
|
19.8 nanogram per liter (ng/L)
Standard Deviation 10.4
|
14.9 nanogram per liter (ng/L)
Standard Deviation 6.10
|
31.3 nanogram per liter (ng/L)
Standard Deviation 12.7
|
108 nanogram per liter (ng/L)
Standard Deviation 130
|
26.4 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
18.0 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
34.7 nanogram per liter (ng/L)
Standard Deviation 22.7
|
18.6 nanogram per liter (ng/L)
Standard Deviation 4.19
|
—
|
23.3 nanogram per liter (ng/L)
Standard Deviation 7.40
|
77.0 nanogram per liter (ng/L)
Standard Deviation 106
|
34.5 nanogram per liter (ng/L)
Standard Deviation 15.6
|
18.9 nanogram per liter (ng/L)
Standard Deviation 3.71
|
84.4 nanogram per liter (ng/L)
Standard Deviation 87.8
|
68.3 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
31.7 nanogram per liter (ng/L)
Standard Deviation 24.2
|
—
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
INF-γ: Cycle 1 Day 5
|
24.7 nanogram per liter (ng/L)
Standard Deviation 10.8
|
29.1 nanogram per liter (ng/L)
Standard Deviation 10.7
|
13.8 nanogram per liter (ng/L)
Standard Deviation 7.71
|
173 nanogram per liter (ng/L)
Standard Deviation 199
|
129 nanogram per liter (ng/L)
Standard Deviation 84.1
|
585 nanogram per liter (ng/L)
Standard Deviation 313
|
335 nanogram per liter (ng/L)
Standard Deviation 74.3
|
209 nanogram per liter (ng/L)
Standard Deviation 191
|
162 nanogram per liter (ng/L)
Standard Deviation 183
|
—
|
48.2 nanogram per liter (ng/L)
Standard Deviation 30.3
|
92.6 nanogram per liter (ng/L)
Standard Deviation 86.4
|
94.3 nanogram per liter (ng/L)
Standard Deviation 103
|
70.9 nanogram per liter (ng/L)
Standard Deviation 54.7
|
64.4 nanogram per liter (ng/L)
Standard Deviation 61.5
|
390 nanogram per liter (ng/L)
Standard Deviation 530
|
279 nanogram per liter (ng/L)
Standard Deviation 526
|
87.7 nanogram per liter (ng/L)
Standard Deviation 42.1
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
INF-γ: Cycle 2 Day 1
|
28.0 nanogram per liter (ng/L)
Standard Deviation 24.1
|
18.3 nanogram per liter (ng/L)
Standard Deviation 3.70
|
12.2 nanogram per liter (ng/L)
Standard Deviation 4.56
|
43.3 nanogram per liter (ng/L)
Standard Deviation 28.4
|
33.9 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
19.8 nanogram per liter (ng/L)
Standard Deviation 4.81
|
15.7 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
43.3 nanogram per liter (ng/L)
Standard Deviation 41.9
|
50.4 nanogram per liter (ng/L)
Standard Deviation 22.7
|
—
|
15.4 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
70.9 nanogram per liter (ng/L)
Standard Deviation 102
|
21.1 nanogram per liter (ng/L)
Standard Deviation 6.39
|
19.7 nanogram per liter (ng/L)
Standard Deviation 3.87
|
62.4 nanogram per liter (ng/L)
Standard Deviation 20.7
|
43.5 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
25.8 nanogram per liter (ng/L)
Standard Deviation 1.04
|
—
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
IL-6: Cycle 2 Day 1
|
41.9 nanogram per liter (ng/L)
Standard Deviation 14.7
|
106 nanogram per liter (ng/L)
Standard Deviation 76.4
|
191 nanogram per liter (ng/L)
Standard Deviation 240
|
883 nanogram per liter (ng/L)
Standard Deviation 570
|
351 nanogram per liter (ng/L)
Standard Deviation 448
|
169 nanogram per liter (ng/L)
Standard Deviation 18.1
|
519 nanogram per liter (ng/L)
Standard Deviation 475
|
311 nanogram per liter (ng/L)
Standard Deviation 447
|
254 nanogram per liter (ng/L)
Standard Deviation 151
|
95.7 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
254 nanogram per liter (ng/L)
Standard Deviation 99.4
|
669 nanogram per liter (ng/L)
Standard Deviation 1075
|
276 nanogram per liter (ng/L)
Standard Deviation 249
|
372 nanogram per liter (ng/L)
Standard Deviation 279
|
282 nanogram per liter (ng/L)
Standard Deviation 176
|
718 nanogram per liter (ng/L)
Standard Deviation 649
|
264 nanogram per liter (ng/L)
Standard Deviation 379
|
—
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
INF-γ: Cycle 2 Day 5
|
31.2 nanogram per liter (ng/L)
Standard Deviation 19.2
|
24.3 nanogram per liter (ng/L)
Standard Deviation 10.8
|
16.3 nanogram per liter (ng/L)
Standard Deviation 8.03
|
53.2 nanogram per liter (ng/L)
Standard Deviation 15.3
|
45.1 nanogram per liter (ng/L)
Standard Deviation 28.5
|
171 nanogram per liter (ng/L)
Standard Deviation 78.4
|
84.8 nanogram per liter (ng/L)
Standard Deviation 58.6
|
141 nanogram per liter (ng/L)
Standard Deviation 139
|
120 nanogram per liter (ng/L)
Standard Deviation 178
|
—
|
60.3 nanogram per liter (ng/L)
Standard Deviation 19.5
|
73.3 nanogram per liter (ng/L)
Standard Deviation 77.7
|
47.7 nanogram per liter (ng/L)
Standard Deviation 43.5
|
38.5 nanogram per liter (ng/L)
Standard Deviation 22.2
|
54.0 nanogram per liter (ng/L)
Standard Deviation 36.1
|
326 nanogram per liter (ng/L)
Standard Deviation 124
|
101 nanogram per liter (ng/L)
Standard Deviation 71.0
|
41.9 nanogram per liter (ng/L)
Standard Deviation 1.42
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
IL-6: Cycle 1 Day 1
|
104 nanogram per liter (ng/L)
Standard Deviation 61.8
|
118 nanogram per liter (ng/L)
Standard Deviation 33.0
|
169 nanogram per liter (ng/L)
Standard Deviation 280
|
938 nanogram per liter (ng/L)
Standard Deviation 845
|
254 nanogram per liter (ng/L)
Standard Deviation 177
|
148 nanogram per liter (ng/L)
Standard Deviation 14.6
|
1826 nanogram per liter (ng/L)
Standard Deviation 3474
|
323 nanogram per liter (ng/L)
Standard Deviation 630
|
211 nanogram per liter (ng/L)
Standard Deviation 143
|
—
|
506 nanogram per liter (ng/L)
Standard Deviation 137
|
667 nanogram per liter (ng/L)
Standard Deviation 1020
|
274 nanogram per liter (ng/L)
Standard Deviation 234
|
306 nanogram per liter (ng/L)
Standard Deviation 181
|
706 nanogram per liter (ng/L)
Standard Deviation 1757
|
200 nanogram per liter (ng/L)
Standard Deviation 101
|
757 nanogram per liter (ng/L)
Standard Deviation 2165
|
—
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
IL-6: Cycle 1 Day 5
|
116 nanogram per liter (ng/L)
Standard Deviation 121
|
113 nanogram per liter (ng/L)
Standard Deviation 51.9
|
223 nanogram per liter (ng/L)
Standard Deviation 229
|
2022 nanogram per liter (ng/L)
Standard Deviation 1491
|
802 nanogram per liter (ng/L)
Standard Deviation 797
|
677 nanogram per liter (ng/L)
Standard Deviation 751
|
5240 nanogram per liter (ng/L)
Standard Deviation 5279
|
699 nanogram per liter (ng/L)
Standard Deviation 538
|
723 nanogram per liter (ng/L)
Standard Deviation 1077
|
151 nanogram per liter (ng/L)
Standard Deviation NA
Standard Deviation could not be calculated for a single participant.
|
524 nanogram per liter (ng/L)
Standard Deviation 180
|
1269 nanogram per liter (ng/L)
Standard Deviation 1807
|
513 nanogram per liter (ng/L)
Standard Deviation 585
|
527 nanogram per liter (ng/L)
Standard Deviation 538
|
273 nanogram per liter (ng/L)
Standard Deviation 244
|
1049 nanogram per liter (ng/L)
Standard Deviation 1288
|
635 nanogram per liter (ng/L)
Standard Deviation 500
|
232 nanogram per liter (ng/L)
Standard Deviation 13.8
|
|
Parts A, B and C: Maximum Cell Count of Interferon-gamma (INF-γ) and Interleukin 6 (IL-6)
IL-6: Cycle 2 Day 5
|
56.2 nanogram per liter (ng/L)
Standard Deviation 19.1
|
95.2 nanogram per liter (ng/L)
Standard Deviation 45.3
|
125 nanogram per liter (ng/L)
Standard Deviation 89.3
|
1145 nanogram per liter (ng/L)
Standard Deviation 700
|
399 nanogram per liter (ng/L)
Standard Deviation 243
|
252 nanogram per liter (ng/L)
Standard Deviation 124
|
1372 nanogram per liter (ng/L)
Standard Deviation 1841
|
341 nanogram per liter (ng/L)
Standard Deviation 252
|
318 nanogram per liter (ng/L)
Standard Deviation 174
|
116 nanogram per liter (ng/L)
Standard Deviation 33.0
|
425 nanogram per liter (ng/L)
Standard Deviation 339
|
929 nanogram per liter (ng/L)
Standard Deviation 1962
|
290 nanogram per liter (ng/L)
Standard Deviation 296
|
269 nanogram per liter (ng/L)
Standard Deviation 155
|
269 nanogram per liter (ng/L)
Standard Deviation 174
|
165 nanogram per liter (ng/L)
Standard Deviation 98.6
|
267 nanogram per liter (ng/L)
Standard Deviation 172
|
123 nanogram per liter (ng/L)
Standard Deviation 19.0
|
Adverse Events
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
Serious events: 2 serious events
Other events: 7 other events
Deaths: 0 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
Serious events: 3 serious events
Other events: 8 other events
Deaths: 0 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
Serious events: 5 serious events
Other events: 12 other events
Deaths: 1 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
Serious events: 5 serious events
Other events: 7 other events
Deaths: 3 deaths
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
Serious events: 11 serious events
Other events: 46 other events
Deaths: 7 deaths
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
Serious events: 12 serious events
Other events: 27 other events
Deaths: 7 deaths
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg +Pembrolizumab 200mg
Serious events: 19 serious events
Other events: 42 other events
Deaths: 7 deaths
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Serious events: 10 serious events
Other events: 26 other events
Deaths: 7 deaths
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Serious events: 11 serious events
Other events: 25 other events
Deaths: 8 deaths
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
Serious events: 14 serious events
Other events: 38 other events
Deaths: 8 deaths
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Serious events: 2 serious events
Other events: 3 other events
Deaths: 1 deaths
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Serious events: 12 serious events
Other events: 21 other events
Deaths: 8 deaths
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
Serious events: 2 serious events
Other events: 2 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=47 participants at risk
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 participants at risk
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 participants at risk
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg +Pembrolizumab 200mg
n=42 participants at risk
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 participants at risk
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 participants at risk
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=43 participants at risk
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 participants at risk
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 participants at risk
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 participants at risk
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Eye disorders
Vitritis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Pneumonia aspiration
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Sepsis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Abdominal pain
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Pain
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Pyrexia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Immune system disorders
Anaphylactic reaction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Reproductive system and breast disorders
Pelvic pain
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Immune thrombocytopenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
COVID-19
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Bacteraemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Cellulitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Ileus
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Hypertransaminasaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Extravasation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Electrocardiogram T wave abnormal
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Troponin I increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Failure to thrive
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Eye disorders
Iritis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Injury, poisoning and procedural complications
Overdose
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Haemorrhage intracranial
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Urosepsis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Abscess neck
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Arthritis infective
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Catheter site infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Peritoneal abscess
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Respiratory tract infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Pyelonephritis acute
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Vascular device infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Immune-mediated enterocolitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Large intestine perforation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Supraventricular extrasystoles
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Cardiac tamponade
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Depressed level of consciousness
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Lethargy
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Metabolic encephalopathy
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Myelopathy
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Syncope
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypovolaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Starvation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Type 1 diabetes mellitus
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Fatigue
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Asthenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Injury, poisoning and procedural complications
Stomal hernia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Injury, poisoning and procedural complications
Vaccination complication
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Biliary obstruction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Immune-mediated hepatitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Hallucination
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Mental status changes
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Immune system disorders
Cytokine release syndrome
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour haemorrhage
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Myositis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Vascular disorders
Embolism arterial
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Urinary tract infection enterococcal
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
Other adverse events
| Measure |
Part A, Dose Escalation: Nemvaleukin Alfa 0.1 mcg/kg
n=5 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 0.1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 0.3 mcg/kg
n=4 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 0.3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 1 mcg/kg
n=7 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 3 mcg/kg
n=8 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 6 mcg/kg
n=12 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 8 mcg/kg
n=3 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 8 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part A, Dose Escalation: Nemvaleukin Alfa 10 mcg/kg
n=7 participants at risk
Participants with advanced solid tumors received nemvaleukin alfa 10 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, Melanoma: Nemvaleukin Alfa 6 mcg/kg
n=47 participants at risk
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part B, Dose Expansion, RCC: Nemvaleukin Alfa 6 mcg/kg
n=27 participants at risk
Participants with RCC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in Cycle 1 (Cycle length = 14 days) and then in Cycle 2 and subsequent cycles (each Cycle length = 21 days) until disease progression or the participant met any discontinuation criteria.
|
Part C, Combination Therapy, Safety Run-in: Nemvaleukin Alfa 1 mcg/kg
n=3 participants at risk
Participants with any tumor type received nemvaleukin alfa 1 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the Participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 1 +Safety Run-in: Nemvaleukin Alfa 3 mcg/kg +Pembrolizumab 200mg
n=42 participants at risk
Participants with PD-1/L1 unapproved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation. The Safety Run-in for nemvaleukin alfa 3 mcg/kg was combined with Cohort 1 of Part C due to same dosing level and regimen.
|
Part C, Combination Therapy, Cohort 2: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 participants at risk
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment pretreated) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 3: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=26 participants at risk
Participants with PD-1/L1 approved tumor types (PD-1/L1 treatment naive) received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Rollover, Cohort 4: Nemvaleukin Alfa 3 mcg/kg + Pembrolizumab 200 mg
n=43 participants at risk
Participants rollover from Parts A or B received nemvaleukin alfa 3 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 5: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=3 participants at risk
Participants with melanoma received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 6: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=21 participants at risk
Participants with NSCLC received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
Part C, Combination Therapy, Cohort 7: Nemvaleukin Alfa 6 mcg/kg + Pembrolizumab 200 mg
n=2 participants at risk
Participants with SCCHN received nemvaleukin alfa 6 mcg/kg IV infusion administration daily from Days 1 to 5 in combination with pembrolizumab 200 mg IV infusion on Day 1 in each Cycle (cycle length = 21 days) for a maximum of 2 years for as long as the participant appeared to be deriving clinical benefit (i.e., objective response or SD) and had tolerated therapy well. Participants could continue nemvaleukin alfa as monotherapy beyond the maximum of 2 years of treatment by switching to monotherapy at the joint discretion of the Investigator and Sponsor and if they did not meet any other criteria for discontinuation.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
40.0%
2/5 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Iron deficiency anaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
3/12 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.8%
4/27 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.1%
6/26 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Renal and urinary disorders
Hydronephrosis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Peripheral swelling
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.8%
4/27 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.0%
31/47 • Number of events 152 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
40.7%
11/27 • Number of events 49 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
8/42 • Number of events 58 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.5%
10/26 • Number of events 68 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
34.9%
15/43 • Number of events 83 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
7/21 • Number of events 33 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Anaemia
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
71.4%
5/7 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
31.9%
15/47 • Number of events 38 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
29.6%
8/27 • Number of events 17 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
31.0%
13/42 • Number of events 35 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.3%
11/26 • Number of events 32 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.2%
13/43 • Number of events 34 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
9/21 • Number of events 38 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Pyrexia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
2/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
71.4%
5/7 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
8/8 • Number of events 24 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
12/12 • Number of events 59 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
70.2%
33/47 • Number of events 104 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
63.0%
17/27 • Number of events 27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
71.4%
30/42 • Number of events 148 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
65.4%
17/26 • Number of events 80 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
61.5%
16/26 • Number of events 45 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.3%
7/43 • Number of events 33 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
47.6%
10/21 • Number of events 37 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
2/2 • Number of events 29 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Chills
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
2/4 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
71.4%
5/7 • Number of events 16 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
8/8 • Number of events 29 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
91.7%
11/12 • Number of events 52 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 32 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
44.7%
21/47 • Number of events 226 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
51.9%
14/27 • Number of events 47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
76.2%
32/42 • Number of events 171 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
61.5%
16/26 • Number of events 62 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
69.2%
18/26 • Number of events 95 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
20.9%
9/43 • Number of events 129 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
61.9%
13/21 • Number of events 65 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
2/2 • Number of events 42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Fatigue
|
80.0%
4/5 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
4/12 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.4%
11/47 • Number of events 28 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
29.6%
8/27 • Number of events 14 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
45.2%
19/42 • Number of events 33 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.3%
11/26 • Number of events 39 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
20.9%
9/43 • Number of events 28 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 11 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
2/2 • Number of events 18 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Oedema peripheral
|
20.0%
1/5 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
8/42 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Asthenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Malaise
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
General disorders
Pain
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Vomiting
|
40.0%
2/5 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
2/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
4/8 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
41.7%
5/12 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 14 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
27.7%
13/47 • Number of events 29 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
35.7%
15/42 • Number of events 27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.5%
10/26 • Number of events 23 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 49 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.1%
8/21 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
2/2 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Nausea
|
40.0%
2/5 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
4/8 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
41.7%
5/12 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
51.1%
24/47 • Number of events 90 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
29.6%
8/27 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
21/42 • Number of events 45 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
13/26 • Number of events 22 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
34.6%
9/26 • Number of events 36 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
18.6%
8/43 • Number of events 64 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
57.1%
12/21 • Number of events 29 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Constipation
|
40.0%
2/5 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
4/8 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.8%
6/47 • Number of events 12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
35.7%
15/42 • Number of events 20 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
5/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
100.0%
3/3 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
26.2%
11/42 • Number of events 12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Diarrhoea
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.8%
6/47 • Number of events 26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
10/42 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.6%
11/43 • Number of events 20 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Abdominal pain upper
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Ascites
|
20.0%
1/5 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Flatulence
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Vascular disorders
Hypotension
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
58.3%
7/12 • Number of events 16 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
57.1%
4/7 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.6%
20/47 • Number of events 65 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
18.5%
5/27 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
18/42 • Number of events 67 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.1%
6/26 • Number of events 11 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 54 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Vascular disorders
Hypertension
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.1%
6/26 • Number of events 18 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Vascular disorders
Embolism
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
2/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood creatinine increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
4/8 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
22.2%
6/27 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
8/42 • Number of events 17 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
36.2%
17/47 • Number of events 27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
22.2%
6/27 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 11 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 17 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.6%
5/43 • Number of events 27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
5/21 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Aspartate aminotransferase increased
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.3%
18/47 • Number of events 27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.9%
7/27 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 19 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.6%
5/43 • Number of events 24 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 20 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
5/21 • Number of events 14 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Weight decreased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
7/42 • Number of events 28 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 24 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood bilirubin increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Weight increased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Lymphopenia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
7/42 • Number of events 51 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.1%
8/21 • Number of events 72 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.4%
11/47 • Number of events 21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.9%
7/27 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
31.0%
13/42 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
13/26 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
3/12 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
8/42 • Number of events 24 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.2%
5/26 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Dehydration
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
40.0%
2/5 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
29.6%
8/27 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
8/42 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.1%
6/26 • Number of events 14 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
52.4%
11/21 • Number of events 40 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.8%
6/47 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.9%
5/42 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Headache
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
3/12 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
27.7%
13/47 • Number of events 26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
22.2%
6/27 • Number of events 40 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
10/42 • Number of events 19 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
30.8%
8/26 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
34.6%
9/26 • Number of events 32 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
18.6%
8/43 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Nervous system disorders
Dizziness
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.8%
6/47 • Number of events 12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
1/5 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
2/12 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.9%
7/47 • Number of events 19 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
7/42 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
37.5%
3/8 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 18 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 13 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
2/8 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 14 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.7%
7/42 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 11 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
1/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.9%
7/47 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
26.9%
7/26 • Number of events 26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
16.3%
7/43 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
25.0%
1/4 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
42.9%
3/7 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
4/12 • Number of events 23 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.9%
7/47 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
18.5%
5/27 • Number of events 18 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
38.1%
16/42 • Number of events 59 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.1%
6/26 • Number of events 24 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.3%
4/43 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 20 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
20.0%
1/5 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.5%
1/8 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.3%
1/12 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
2/7 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
10/42 • Number of events 42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
66.7%
2/3 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Cardiac disorders
Palpitations
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
COVID-19
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
8.5%
4/47 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.9%
5/42 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Injury, poisoning and procedural complications
Infusion related reaction
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
18.5%
5/27 • Number of events 17 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 18 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 19 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
Blood pressure
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
12.8%
6/47 • Number of events 25 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
22.2%
6/27 • Number of events 11 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/42 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Investigations
White blood cell count decreased
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.3%
2/47 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.4%
2/27 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
6/42 • Number of events 73 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 53 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
28.6%
6/21 • Number of events 35 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
10.6%
5/47 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.7%
1/27 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/21 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.1%
1/47 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.8%
4/27 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
2/42 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.0%
3/43 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.9%
5/42 • Number of events 15 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.8%
1/21 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.9%
5/42 • Number of events 7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
23.8%
5/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.4%
1/42 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
15.4%
4/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
4.7%
2/43 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Respiratory, thoracic and mediastinal disorders
Tachypnoea
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 10 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
4/42 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
2.3%
1/43 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
9.5%
2/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
6.4%
3/47 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.1%
3/27 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
33.3%
1/3 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 9 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
3.8%
1/26 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.5%
3/26 • Number of events 4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
11.6%
5/43 • Number of events 8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
19.0%
4/21 • Number of events 6 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
|
Infections and infestations
Pneumonia
|
0.00%
0/5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/4 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/8 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/12 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/7 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/47 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/27 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.1%
3/42 • Number of events 3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
7.7%
2/26 • Number of events 2 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/26 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/43 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
0.00%
0/3 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
14.3%
3/21 • Number of events 5 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
50.0%
1/2 • Number of events 1 • From first dose of study drug until 30 days after last dose (up to 10 months for Part A; up to 41.3 months for Part B; up to 51.5 months for Part C)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER