Trial Outcomes & Findings for Efficacy and Safety Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Adults With Selected Advanced/Metastatic Solid Tumors (MK-7123-034) (NCT NCT03473925)
NCT ID: NCT03473925
Last Updated: 2024-08-28
Results Overview
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was estimated using an exact method based on the binomial distribution, and the 95% confidence interval was estimated by the method of Clopper-Pearson.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
107 participants
Primary outcome timeframe
Up to approximately 2 years
Results posted on
2024-08-28
Participant Flow
Adults with one of the following types of solid tumors: Programmed Death-Ligand 1 (PD-L1) positive refractory non-small cell lung cancer (NSCLC), castration resistant prostate cancer (CRPC) or microsatellite stable (MSS) colorectal cancer (CRC), were enrolled in this study.
Participant milestones
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Overall Study
STARTED
|
52
|
55
|
|
Overall Study
Treated
|
51
|
54
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
52
|
55
|
Reasons for withdrawal
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Overall Study
Death
|
48
|
44
|
|
Overall Study
Sponsor Decision
|
2
|
7
|
|
Overall Study
Withdrawal by Subject
|
1
|
3
|
|
Overall Study
Not Treated
|
1
|
1
|
Baseline Characteristics
Efficacy and Safety Study of Navarixin (MK-7123) in Combination With Pembrolizumab (MK-3475) in Adults With Selected Advanced/Metastatic Solid Tumors (MK-7123-034)
Baseline characteristics by cohort
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
64.1 Years
STANDARD_DEVIATION 13.3 • n=5 Participants
|
62.8 Years
STANDARD_DEVIATION 13.0 • n=7 Participants
|
63.4 Years
STANDARD_DEVIATION 13.1 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
27 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
41 Participants
n=7 Participants
|
78 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
49 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
103 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
14 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
36 Participants
n=5 Participants
|
39 Participants
n=7 Participants
|
75 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine.
ORR is defined as the percentage of participants who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR was estimated using an exact method based on the binomial distribution, and the 95% confidence interval was estimated by the method of Clopper-Pearson.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Objective Response Rate (ORR) Based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
|
3.9 Percentage of participants
Interval 0.5 to 13.5
|
1.9 Percentage of participants
Interval 0.0 to 9.9
|
PRIMARY outcome
Timeframe: Up to 21 daysPopulation: Participants who complete cycle 1 without any discontinuation, or discontinues from the study prior to completing all the safety evaluations in cycle 1 due to treatment-related adverse events, or if participants receive \>=75% of the total pembrolizumab infusion and/or navarixin in cycle, or If the participants experience any DLT in AE.
The following toxicities are considered a DLT, assessed as related to study treatment: Grade 4 non-hematologic toxicity, Grade 4 anemia, Grade 3 anemia lasting \>7 days or requiring transfusion, Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia, a) Grade 4 thrombocytopenia of any duration, b) Grade 3 thrombocytopenia associated with bleeding, Grade 3 non-hematologic toxicity lasting \>3 days, any Grade 3 or Grade 4 non-hematologic laboratory value if: medical intervention is required or the abnormality leads to hospitalization or persists for \>72 hours, Liver test abnormalities: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>3X Upper Limit of Normal (ULN) with total bilirubin (TBL) \>2X ULN with no elevation in alkaline phosphatase (AP \<2X ULN), Grade 3 or Grade 4 febrile neutropenia, inability to administer ≥75% of the planned navarixin dose due to drug-related tolerability, delay in Cycle 2 start by \>2 weeks due to toxicity
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=48 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=48 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Number of Participants With Dose-limiting Toxicities (DLTs) During Treatment Cycle 1
|
2 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 27 monthsPopulation: All participants who received at least 1 dose of study treatment.
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Number of Participants Who Experience at Least One Adverse Event (AE)
|
50 Participants
|
54 Participants
|
PRIMARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants who received at least 1 dose of study treatment.
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Number of Participants Who Discontinue Study Treatment Due to an AE
|
4 Participants
|
6 Participants
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine. Only participants with progressive disease per RECIST 1.1 are included.
An objective response is defined as an immune-based Complete Response (iCR: Disappearance of all target lesions) or immune-based Partial Response (iPR: At least a 30% decrease in the sum of diameters of target lesions). ORR will be assessed by the investigator based on iRECIST following administration of navarixin in combination with pembrolizumab. The percentage of participants with progressive disease per RECIST 1.1 who experience an iCR or iPR are presented.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=43 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=41 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)
iComplete Response (iCR)
|
0.0 Percentage of participants
Interval 0.0 to 8.2
|
0.0 Percentage of participants
Interval 0.0 to 8.6
|
|
Objective Response Rate (ORR) Per Modified RECIST 1.1 for Immune-based Therapeutics (iRECIST)
iPartial Response (iPR)
|
0.0 Percentage of participants
Interval 0.0 to 8.2
|
0.0 Percentage of participants
Interval 0.0 to 8.6
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine.
PFS is defined as the time from the first dose of study treatment to the first confirmed documented disease progression, or death due to any cause, whichever occurs first. Per RECIST 1.1, progressive disease is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions is also considered progression. Median PFS per RECIST 1.1 was assessed by the investigator from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-\[L\]1) refractory non-small cell lung cancer (NSCLC).
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Progression-free Survival (PFS) Per RECIST 1.1
CRC
|
1.8 Months
Interval 1.0 to 2.0
|
1.9 Months
Interval 1.6 to 2.0
|
|
Progression-free Survival (PFS) Per RECIST 1.1
CRPC
|
2.1 Months
Interval 1.9 to 4.1
|
2.1 Months
Interval 1.9 to 4.5
|
|
Progression-free Survival (PFS) Per RECIST 1.1
NSCLC
|
2.4 Months
Interval 1.6 to 10.2
|
2.1 Months
Interval 1.9 to 2.4
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine.
PFS is defined as the time from the first dose of study treatment to the first documented disease progression or death due to any cause, whichever occurs first. Per iRECIST, progressive disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions. Disease progression is to be confirmed by a consecutive assessment at least 4-8 weeks after first documentation and will be assessed by the investigator. Median PFS per iRECIST was assessed by the investigator from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-\[L\]1) refractory non-small cell lung cancer (NSCLC).
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
PFS Per iRECIST
CRC
|
4.1 Months
Interval 2.1 to 7.1
|
6.2 Months
Interval 3.3 to 14.4
|
|
PFS Per iRECIST
CRPC
|
7.9 Months
Interval 5.0 to 8.6
|
5.2 Months
Interval 3.0 to 11.5
|
|
PFS Per iRECIST
NSCLC
|
11.9 Months
Interval 3.2 to 17.5
|
7.0 Months
Interval 2.4 to 14.4
|
SECONDARY outcome
Timeframe: Up to approximately 2 yearsPopulation: All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least 1 dose of study medicine.
OS is defined as the time from the first dose of study treatment to death due to any cause. Median OS was assessed from product-limit (Kaplan-Meier) method for censored data in participants with microsatellite stable colorectal cancer (CRC); with castration-resistant prostate cancer (CRPC), and with programmed cell death ligand 1 (PD-\[L\]1) refractory non-small cell lung cancer (NSCLC).
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Overall Survival (OS)
CRC
|
6.5 Months
Interval 3.0 to 9.7
|
8.0 Months
Interval 5.7 to 14.4
|
|
Overall Survival (OS)
CRPC
|
10.8 Months
Interval 7.9 to 13.4
|
11.2 Months
Interval 3.7 to 23.0
|
|
Overall Survival (OS)
MSCLC
|
13.0 Months
Interval 3.2 to 18.0
|
12.0 Months
Interval 2.4 to 19.9
|
SECONDARY outcome
Timeframe: Day 3: PredosePopulation: Participants who complied with the protocol sufficiently to ensure that their data will be likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes such considerations as exposure to treatment, availability of measurements, and the absence of major protocol violations
Peripheral blood neutrophil counts were performed at Cycle 1 Day 3: Predose, to determine the concentration of ANC.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=50 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=51 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Absolute Neutrophil Counts (ANC)
|
3.6 10^9 cells/L
Interval 3.03 to 4.12
|
3.2 10^9 cells/L
Interval 2.5 to 3.84
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose; Cycle 1 Days 3 & 8: Predose & 6-12 hours postdose; Cycle 2 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose (Up to approximately 23 days)Population: Participants with available AUC-inf data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.
Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-inf
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=38 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=27 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Navarixin Area Under the Plasma Concentration-Time Curve (AUC) From Time 0 to Infinity (AUC0-inf)
|
523 h*ng/mL
Geometric Coefficient of Variation 39.5
|
1200 h*ng/mL
Geometric Coefficient of Variation 47.5
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose; Cycle 1 Days 3 & 8: Predose & 6-12 hours postdose; Cycle 2 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose(Up to approximately 23 days)Population: Participants with available AUC-last data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.
Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma AUC0-last.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=45 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=46 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Navarixin Area Under the Plasma Concentration-Time Curve From Time 0 to Last (AUC0-last)
|
451 h*ng/mL
Geometric Coefficient of Variation 35.7
|
961 h*ng/mL
Geometric Coefficient of Variation 45.9
|
SECONDARY outcome
Timeframe: Cycle 1 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose; Cycle 1 Days 3 & 8: Predose & 6-12 hours postdose; Cycle 2 Day 1: Predose & 1, 2, 4, 6 & 8-12 hours postdose (Up to approximately 23 days)Population: Participants with available Cmax data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.
Plasma samples from participants with selected advanced/metastatic solid tumors were collected to determine the navarixin plasma Cmax.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=45 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=46 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Navarixin Maximum Plasma Concentration (Cmax)
|
172 ng/mL
Geometric Coefficient of Variation 53.3
|
288 ng/mL
Geometric Coefficient of Variation 60.6
|
SECONDARY outcome
Timeframe: Cycle 2 Day 21 (Up to approximately 43 days)Population: Participants with available Ctrough data, who complied with the protocol sufficiently to ensure that their data was likely to exhibit the effects of treatment, according to the underlying scientific model. Compliance includes, but is not limited to, exposure to treatment, availability of measurements, and absence of major protocol violations.
Plasma samples from participants with selected advanced/metastatic solid tumors were collected at steady state on Cycle 2 Day 21 to determine navarixin Ctrough. The Arithmetic Mean and CV% are presented.
Outcome measures
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=36 Participants
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=35 Participants
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Navarixin Trough Plasma Concentration (Ctrough)
|
NA ng/mL
Geometric Coefficient of Variation NA
Measure Type - Arithmetic Mean: 7.71
Measure of Dispersion - CV%: 10.7%
|
NA ng/mL
Geometric Coefficient of Variation NA
Measure Type - Arithmetic Mean: 14.5
Measure of Dispersion - CV%: 77.3%
|
Adverse Events
Navarixin 30 mg + Pembrolizumab 200 mg
Serious events: 17 serious events
Other events: 48 other events
Deaths: 48 deaths
Navarixin 100 mg + Pembrolizumab 200 mg
Serious events: 15 serious events
Other events: 52 other events
Deaths: 45 deaths
Serious adverse events
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 participants at risk
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 participants at risk
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Gastrointestinal disorders
Colitis
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Intestinal fistula
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
General physical health deterioration
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Pyrexia
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Lower respiratory tract infection
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
7.8%
4/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Pseudomonas infection
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Injury, poisoning and procedural complications
Humerus fracture
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Injury, poisoning and procedural complications
Spinal compression fracture
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Neutrophil count decreased
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Transaminases increased
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Cachexia
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Encephalopathy
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Completed suicide
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Suicide attempt
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Renal impairment
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis exfoliative
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
Other adverse events
| Measure |
Navarixin 30 mg + Pembrolizumab 200 mg
n=51 participants at risk
Participants received 30 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
Navarixin 100 mg + Pembrolizumab 200 mg
n=54 participants at risk
Participants received 100 mg navarixin via oral capsules once daily, plus 200 mg pembrolizumab via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years).
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
13.7%
7/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Blood and lymphatic system disorders
Neutropenia
|
9.8%
5/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
16.7%
9/54 • Number of events 12 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Endocrine disorders
Hypothyroidism
|
3.9%
2/51 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
17.6%
9/51 • Number of events 10 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Constipation
|
13.7%
7/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
13.0%
7/54 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
9.8%
5/51 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
13.0%
7/54 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
7.8%
4/51 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
17.6%
9/51 • Number of events 9 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
29.6%
16/54 • Number of events 17 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
9.8%
5/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
18.5%
10/54 • Number of events 10 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Asthenia
|
9.8%
5/51 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
7.4%
4/54 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Chills
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Fatigue
|
33.3%
17/51 • Number of events 18 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
25.9%
14/54 • Number of events 14 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Oedema peripheral
|
7.8%
4/51 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
7.4%
4/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
General disorders
Pyrexia
|
23.5%
12/51 • Number of events 18 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
22.2%
12/54 • Number of events 16 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Pneumonia
|
5.9%
3/51 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
3.7%
2/54 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Urinary tract infection
|
9.8%
5/51 • Number of events 9 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
9.8%
5/51 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
7.4%
4/54 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Blood alkaline phosphatase increased
|
5.9%
3/51 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
7.4%
4/54 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Blood creatinine increased
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Neutrophil count decreased
|
13.7%
7/51 • Number of events 11 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
18.5%
10/54 • Number of events 13 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
Weight decreased
|
11.8%
6/51 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Investigations
White blood cell count decreased
|
5.9%
3/51 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
27.5%
14/51 • Number of events 14 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
14.8%
8/54 • Number of events 8 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Dehydration
|
7.8%
4/51 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
13.0%
7/54 • Number of events 9 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
3.9%
2/51 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.9%
2/51 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
11.8%
6/51 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
16.7%
9/54 • Number of events 11 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.8%
6/51 • Number of events 6 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
18.5%
10/54 • Number of events 11 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
7.4%
4/54 • Number of events 4 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Headache
|
15.7%
8/51 • Number of events 8 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
13.0%
7/54 • Number of events 8 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Dysuria
|
9.8%
5/51 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
0.00%
0/54 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.6%
10/51 • Number of events 12 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
14.8%
8/54 • Number of events 9 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
17.6%
9/51 • Number of events 10 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.9%
3/51 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 2 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.9%
3/51 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
1.9%
1/54 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/51 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
5.6%
3/54 • Number of events 3 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.7%
8/51 • Number of events 11 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
11.1%
6/54 • Number of events 7 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.0%
1/51 • Number of events 1 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
9.3%
5/54 • Number of events 5 • All-cause mortality: From randomization up to approximately 27 months; Adverse Events (AEs) from first treatment up to approximately 27 months
All-Cause Mortality was reported for all randomized participants. AEs were reported for all participants who received at least 1 dose of study treatment.
|
Additional Information
Senior Vice President, Global Clinical Development
Merck Sharp & Dohme LLC
Phone: 1-800-672-6372
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee If publication activity is not directed by the sponsor, the investigator agrees to submit all manuscripts or abstracts to the sponsor before submission.
- Publication restrictions are in place
Restriction type: OTHER