Study of Pembrolizumab (MK-3475) vs Standard Therapy in Participants With Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) Stage IV Colorectal Carcinoma (MK-3475-177/KEYNOTE-177)
Study Details
Study Description
Brief Summary
In this study, participants with stage IV Microsatellite Instability-High (MSI-H) or Mismatch Repair Deficient (dMMR) colorectal carcinoma (CRC) will be randomly assigned to receive either pembrolizumab or the Investigator's choice of 1 of 6 standard of care (SOC) chemotherapy regimens for the treatment of advanced colorectal carcinoma. The primary study hypothesis is that pembrolizumab will prolong progression-free survival (PFS) or overall survival (OS) compared to current SOC chemotherapy.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Pembrolizumab Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Participants that have stopped the initial course of pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional). |
Biological: pembrolizumab
MK-3475 SCH 900475 KEYTRUDA®
Other Names:
|
Active Comparator: Standard of Care (SOC) Participants receive 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Participants that have stopped pembrolizumab and have stable disease but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 year additional). |
Drug: mFOLFOX6
Regimen consists of oxaliplatin 85 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-fluorouracil (5-FU) 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle
Drug: FOLFIRI
Regimen consists of irinotecan 180 mg/m^2 IV on Day 1, leucovorin 400 mg/m^2 or levoleucovorin 200 mg/m^2 IV on Day 1, 5-FU 400 mg/m^2 IV bolus on Day 1 and then 1200 mg/m^2/day IV over 2 days for total dose of 2400 mg/m^2 in each 2-week cycle
Biological: pembrolizumab
MK-3475 SCH 900475 KEYTRUDA®
Other Names:
Biological: bevacizumab
Other Names:
Biological: cetuximab
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) Per RECIST1.1 As Assessed by Central Imaging Vendor [Up to approximately 59 months]
PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Hazards ratio (HR) and associated 95% confidence intervals (CIs) from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
- Overall Survival (OS) [Up to approximately 59 months]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. HR and associated 95% CIs from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol.
Secondary Outcome Measures
- Overall Response Rate (ORR) Per RECIST1.1 as Assessed by Central Imaging Vendor [Up to approximately 59 months]
ORR was defined as the percentage of the participants who experienced 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) and was assessed using RECIST 1.1 as assessed by the central imaging vendor. The percentage of participants who experienced a CR or PR was presented for the first course of study treatment per protocol.
- Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 59 months]
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course study treatment per protocol.
- Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 59 months]
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented for the first course study treatment per protocol.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Locally confirmed dMMR or MSI-H stage IV colorectal carcinoma
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 10 days prior to study start
-
Life expectancy of at least 3 months
-
Measurable disease
-
Female participants of childbearing potential must be willing to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of standard of care (SOC) therapy or 120 days after the last pembrolizumab dose
-
Male participants must agree to use adequate contraception for the course of the study starting with the first dose of study medication through 180 days after the last dose of SOC therapy or 120 days after the last pembrolizumab dose
-
Adequate organ function
Exclusion Criteria:
-
Has received prior systemic therapy for Stage IV colorectal cancer. May have received prior adjuvant chemotherapy for colorectal cancer as long as it was completed at least 6 months prior to randomization on this study
-
Currently participating and receiving treatment in another study, or participated in a study of an investigational agent and received treatment, or used an investigational device within 4 weeks of randomization
-
Active autoimmune disease that has required systemic treatment in past 2 years
-
Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to randomization on this study
-
Radiation therapy within 4 weeks prior to randomization on this study and not recovered to baseline from adverse events due to radiation therapy
-
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
-
Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization on this study
-
Has received prior therapy with an immune checkpoint inhibitor (e.g., anti-programmed cell death [PD]-1, anti-PD ligand 1 [L1], anti-PD-L2 agent, or anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] agent, etc.)
-
Another malignancy that is progressing or requires active treatment with the exception of non-melanomatous skin cancer that has undergone potentially curative therapy and in situ cervical carcinoma
-
Received a live vaccine within 30 days of planned start of study medication
-
Known history of Human Immunodeficiency Virus (HIV), Hepatitis B or C
-
Known history of, or any evidence of interstitial lung disease or active, non-infectious pneumonitis
-
Known history of active tuberculosis (Bacillus tuberculosis [TB])
-
Active infection requiring systemic therapy
-
Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
-
Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of SOC or 120 days after the last dose of pembrolizumab
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- 3475-177
- 2015-002024-89
- 163238
- MK-3475-177
- KEYNOTE-177
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Of the 307 participants randomized in the study, 296 participants received study medication and were evaluable for safety analyses. |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Period Title: Overall Study | ||
STARTED | 153 | 154 |
Treated | 153 | 143 |
Received Second Course of Pembrolizumab | 8 | 4 |
Switched Over to Pembrolizumab | 0 | 56 |
COMPLETED | 0 | 0 |
NOT COMPLETED | 153 | 154 |
Baseline Characteristics
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) | Total |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Total of all reporting groups |
Overall Participants | 153 | 154 | 307 |
Age (Years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [Years] |
61.9
(14.9)
|
60.6
(14.8)
|
61.2
(14.8)
|
Sex: Female, Male (Count of Participants) | |||
Female |
82
53.6%
|
72
46.8%
|
154
50.2%
|
Male |
71
46.4%
|
82
53.2%
|
153
49.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||
Hispanic or Latino |
11
7.2%
|
10
6.5%
|
21
6.8%
|
Not Hispanic or Latino |
128
83.7%
|
131
85.1%
|
259
84.4%
|
Unknown or Not Reported |
14
9.2%
|
13
8.4%
|
27
8.8%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
24
15.7%
|
26
16.9%
|
50
16.3%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
9
5.9%
|
5
3.2%
|
14
4.6%
|
White |
113
73.9%
|
116
75.3%
|
229
74.6%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
7
4.6%
|
7
4.5%
|
14
4.6%
|
Outcome Measures
Title | Progression-Free Survival (PFS) Per RECIST1.1 As Assessed by Central Imaging Vendor |
---|---|
Description | PFS was defined as the time from randomization to the first documented disease progression (PD) per RECIST 1.1 based on blinded central imaging vendor review or death due to any cause, whichever occurs first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum had to demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. Hazards ratio (HR) and associated 95% confidence intervals (CIs) from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol. |
Time Frame | Up to approximately 59 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Measure Participants | 153 | 154 |
Median (95% Confidence Interval) [Months] |
16.5
|
8.2
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Standard of Care (SOC) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0001 |
Comments | ||
Method | Log Rank | |
Comments | One-sided p-value based on log rank test | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.59 | |
Confidence Interval |
(2-Sided) 95% 0.45 to 0.79 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Based on Cox regression model with Efron's method of tie handling with treatment as a covariate. |
Title | Overall Survival (OS) |
---|---|
Description | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of analysis were censored at the date of last known contact. HR and associated 95% CIs from a Cox proportional hazard model with Efron's method of tie handling and with a single treatment covariate was presented for the first course study treatment per protocol. |
Time Frame | Up to approximately 59 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Measure Participants | 153 | 154 |
Median (95% Confidence Interval) [Months] |
NA
|
36.7
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Standard of Care (SOC) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0359 |
Comments | ||
Method | Log Rank | |
Comments | One-sided p-value based on log rank test | |
Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
Estimated Value | 0.74 | |
Confidence Interval |
(2-Sided) 95% 0.53 to 1.03 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Based on Cox regression model with Efron's method of tie handling with treatment as a covariate. |
Title | Overall Response Rate (ORR) Per RECIST1.1 as Assessed by Central Imaging Vendor |
---|---|
Description | ORR was defined as the percentage of the participants who experienced 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) and was assessed using RECIST 1.1 as assessed by the central imaging vendor. The percentage of participants who experienced a CR or PR was presented for the first course of study treatment per protocol. |
Time Frame | Up to approximately 59 months |
Outcome Measure Data
Analysis Population Description |
---|
All randomized participants |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Measure Participants | 153 | 154 |
Number (95% Confidence Interval) [Percentage of Participants] |
45.1
29.5%
|
33.1
21.5%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Pembrolizumab, Standard of Care (SOC) |
---|---|---|
Comments | ||
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.0159 |
Comments | One-sided p-value based on Miettinen & Nurminen method. | |
Method | Miettinen & Nurminen method | |
Comments | ||
Method of Estimation | Estimation Parameter | Difference in percentage |
Estimated Value | 12.0 | |
Confidence Interval |
(2-Sided) 95% 1.0 to 22.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Based on Miettinen & Nurminen method. |
Title | Number of Participants Who Experienced an Adverse Event (AE) |
---|---|
Description | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE was presented for the first course study treatment per protocol. |
Time Frame | Up to approximately 59 months |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least 1 dose of study treatment |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Measure Participants | 153 | 143 |
Count of Participants [Participants] |
149
97.4%
|
142
92.2%
|
Title | Number of Participants Who Discontinued Study Treatment Due to an AE |
---|---|
Description | An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Any worsening (i.e., any clinically significant adverse change infrequency and/or intensity) of a preexisting condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE was presented for the first course study treatment per protocol. |
Time Frame | Up to approximately 59 months |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least 1 dose of study treatment |
Arm/Group Title | Pembrolizumab | Standard of Care (SOC) |
---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). Eligible participants who stopped the initial course of pembrolizumab due to complete response (CR) or completed initial course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. Participants with documented disease progression following chemotherapy can crossover to receive pembrolizumab for up to 35 cycles (approximately 2 years). Eligible cross over participants who stopped pembrolizumab who stopped pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). |
Measure Participants | 153 | 143 |
Count of Participants [Participants] |
21
13.7%
|
20
13%
|
Adverse Events
Time Frame | Up to approximately 59 months | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | All-cause mortality (ACM)=all randomized participants. AEs=all participants who received ≥1 dose of study treatment. Per protocol, disease progression was not considered an AE unless related to treatment. Medical Dictionary for Regulatory Activities (MedDRA) terms neoplasm progression (NP), malignant NP, and disease progression not related to treatment are excluded. Per protocol, collection of AEs and ACM were planned to be done in first and second courses. | |||||||||
Arm/Group Title | Pembrolizumab First Course | Standard of Care (SOC) First Course | SOC Switched Over to Pembrolizumab | Pembrolizumab-Second Course | SOC Switched Over to Pembrolizumab-Second Course | |||||
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 treatments (approximately 2 years). | Participants received 1 of 6 possible standard chemotherapy regimens: mFOLFOX6, or mFOLFOX6+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or mFOLFOX6+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle, or FOLFIRI, or FOLFIRI+bevacizumab 5 mg/kg IV on Day 1 of each 2-week cycle, or FOLFIRI+cetuximab 400 mg/m^2 IV over 2 hours then 250 mg/m^2 over 1 hour weekly in each 2-week cycle. | Eligible participants with documented disease progression following chemotherapy in SOC arm switched over to receive pembrolizumab for up to 35 cycles (approximately 2 years). | Participants who received pembrolizumab as a first course and stopped the first course of pembrolizumab due to complete response (CR) or completed the first course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | Participants who switched over from SOC and received pembrolizumab and subsequently stopped the first course of pembrolizumab due to complete response (CR) or completed the first course of pembrolizumab and had stable disease but progressed after discontinuation, initiated a second course of pembrolizumab at the investigator's discretion for up to 17 cycles (approximately 1 year additional). | |||||
All Cause Mortality |
||||||||||
Pembrolizumab First Course | Standard of Care (SOC) First Course | SOC Switched Over to Pembrolizumab | Pembrolizumab-Second Course | SOC Switched Over to Pembrolizumab-Second Course | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 62/153 (40.5%) | 54/154 (35.1%) | 24/56 (42.9%) | 0/8 (0%) | 0/4 (0%) | |||||
Serious Adverse Events |
||||||||||
Pembrolizumab First Course | Standard of Care (SOC) First Course | SOC Switched Over to Pembrolizumab | Pembrolizumab-Second Course | SOC Switched Over to Pembrolizumab-Second Course | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 62/153 (40.5%) | 75/143 (52.4%) | 27/56 (48.2%) | 2/8 (25%) | 1/4 (25%) | |||||
Blood and lymphatic system disorders | ||||||||||
Anaemia | 1/153 (0.7%) | 1 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Febrile neutropenia | 1/153 (0.7%) | 1 | 6/143 (4.2%) | 6 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Leukocytosis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neutropenia | 0/153 (0%) | 0 | 3/143 (2.1%) | 3 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Thrombocytopenia | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cardiac disorders | ||||||||||
Acute coronary syndrome | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Acute myocardial infarction | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Angina pectoris | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Atrial fibrillation | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cardiac arrest | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Myocardial infarction | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Supraventricular tachycardia | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Endocrine disorders | ||||||||||
Addison's disease | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Adrenal insufficiency | 2/153 (1.3%) | 2 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Adrenocortical insufficiency acute | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Autoimmune thyroiditis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Eye disorders | ||||||||||
Angle closure glaucoma | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vision blurred | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal disorders | ||||||||||
Abdominal pain | 7/153 (4.6%) | 9 | 2/143 (1.4%) | 2 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Abdominal pain upper | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Anal fistula | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Autoimmune colitis | 2/153 (1.3%) | 2 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Colitis | 3/153 (2%) | 3 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Constipation | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Diarrhoea | 4/153 (2.6%) | 4 | 9/143 (6.3%) | 9 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Diarrhoea haemorrhagic | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Diverticular perforation | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Duodenal perforation | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Duodenal ulcer | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Faecaloma | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastritis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal haemorrhage | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal inflammation | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Ileus | 1/153 (0.7%) | 1 | 3/143 (2.1%) | 3 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Impaired gastric emptying | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Intestinal obstruction | 2/153 (1.3%) | 2 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Intestinal perforation | 0/153 (0%) | 0 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Intra-abdominal haemorrhage | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Large intestinal obstruction | 1/153 (0.7%) | 1 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Large intestine perforation | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pancreatitis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Short-bowel syndrome | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Small intestinal obstruction | 2/153 (1.3%) | 2 | 5/143 (3.5%) | 9 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Subileus | 2/153 (1.3%) | 2 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Upper gastrointestinal haemorrhage | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vomiting | 1/153 (0.7%) | 1 | 4/143 (2.8%) | 4 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
General disorders | ||||||||||
Asthenia | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Chest pain | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Death | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Device related thrombosis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Fatigue | 0/153 (0%) | 0 | 3/143 (2.1%) | 3 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gait disturbance | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
General physical health deterioration | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Mucosal inflammation | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Oedema peripheral | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pyrexia | 4/153 (2.6%) | 4 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hepatobiliary disorders | ||||||||||
Acute hepatic failure | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Autoimmune hepatitis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Bile duct stenosis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Biliary dilatation | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholangitis | 0/153 (0%) | 0 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholangitis acute | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholecystitis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholecystitis acute | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholestasis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hepatic failure | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hepatitis | 2/153 (1.3%) | 2 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Immune-mediated hepatitis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Jaundice cholestatic | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Immune system disorders | ||||||||||
Cytokine release syndrome | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypersensitivity | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Infections and infestations | ||||||||||
Abdominal sepsis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
COVID-19 | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Cellulitis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cholecystitis infective | 0/153 (0%) | 0 | 1/143 (0.7%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Clostridium difficile colitis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Clostridium difficile infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Device related infection | 0/153 (0%) | 0 | 2/143 (1.4%) | 3 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Diverticulitis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Endophthalmitis | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Escherichia pyelonephritis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Escherichia sepsis | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastroenteritis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Infection | 2/153 (1.3%) | 3 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Influenza | 1/153 (0.7%) | 1 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Lower respiratory tract infection | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Lymph gland infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Meningoencephalitis viral | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pelvic infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pneumonia | 3/153 (2%) | 3 | 2/143 (1.4%) | 2 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pneumonia streptococcal | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pyelonephritis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pyelonephritis acute | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Respiratory tract infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Sepsis | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Stoma site abscess | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Stoma site infection | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Urinary tract infection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Urosepsis | 0/153 (0%) | 0 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vascular device infection | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Viral infection | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||
Accidental overdose | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal stoma complication | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Head injury | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hip fracture | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Stoma site haemorrhage | 0/153 (0%) | 0 | 1/143 (0.7%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Subdural haematoma | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Tibia fracture | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Urinary tract stoma complication | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Investigations | ||||||||||
Liver function test increased | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neutrophil count decreased | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Norovirus test positive | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||
Decreased appetite | 0/153 (0%) | 0 | 3/143 (2.1%) | 3 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Dehydration | 0/153 (0%) | 0 | 4/143 (2.8%) | 7 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Failure to thrive | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hyperglycaemia | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypoalbuminaemia | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypoglycaemia | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Hypokalaemia | 0/153 (0%) | 0 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypomagnesaemia | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hyponatraemia | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Type 2 diabetes mellitus | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||
Arthralgia | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Autoimmune arthritis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Back pain | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Myositis | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pain in jaw | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
Basal cell carcinoma | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Bladder neoplasm | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Breast cancer | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cancer pain | 1/153 (0.7%) | 2 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Infected neoplasm | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Lung carcinoma cell type unspecified recurrent | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Oropharyngeal cancer | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Rectal adenoma | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Rectal neoplasm | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Squamous cell carcinoma | 2/153 (1.3%) | 4 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Tumour associated fever | 0/153 (0%) | 0 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vaginal neoplasm | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Nervous system disorders | ||||||||||
Amnesia | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Aphasia | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Carotid artery stenosis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cerebral infarction | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cerebral ischaemia | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Cerebrovascular accident | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Occipital neuralgia | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pseudobulbar palsy | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Syncope | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Transient ischaemic attack | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Psychiatric disorders | ||||||||||
Confusional state | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Depression | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Suicide attempt | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Renal and urinary disorders | ||||||||||
Acute kidney injury | 3/153 (2%) | 3 | 2/143 (1.4%) | 2 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 1/4 (25%) | 1 |
Autoimmune nephritis | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Glomerulonephritis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hydronephrosis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Prerenal failure | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Renal failure | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Renal impairment | 1/153 (0.7%) | 2 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Aspiration | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Chronic obstructive pulmonary disease | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Dyspnoea | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hyperventilation | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Interstitial lung disease | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pneumonitis | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pulmonary embolism | 1/153 (0.7%) | 1 | 4/143 (2.8%) | 4 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Respiratory failure | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||
Diabetic foot | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Rash | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Skin erosion | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Skin ulcer | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vascular disorders | ||||||||||
Aortic dissection | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Deep vein thrombosis | 1/153 (0.7%) | 1 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Embolism | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypertension | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Superior vena cava syndrome | 0/153 (0%) | 0 | 1/143 (0.7%) | 1 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||
Pembrolizumab First Course | Standard of Care (SOC) First Course | SOC Switched Over to Pembrolizumab | Pembrolizumab-Second Course | SOC Switched Over to Pembrolizumab-Second Course | ||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 145/153 (94.8%) | 142/143 (99.3%) | 52/56 (92.9%) | 8/8 (100%) | 2/4 (50%) | |||||
Blood and lymphatic system disorders | ||||||||||
Anaemia | 26/153 (17%) | 32 | 32/143 (22.4%) | 39 | 8/56 (14.3%) | 17 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Leukopenia | 0/153 (0%) | 0 | 3/143 (2.1%) | 12 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 1/4 (25%) | 1 |
Neutropenia | 3/153 (2%) | 4 | 27/143 (18.9%) | 52 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Thrombocytopenia | 1/153 (0.7%) | 1 | 8/143 (5.6%) | 18 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 1/4 (25%) | 1 |
Cardiac disorders | ||||||||||
Atrial fibrillation | 3/153 (2%) | 3 | 2/143 (1.4%) | 2 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Endocrine disorders | ||||||||||
Hyperthyroidism | 6/153 (3.9%) | 6 | 0/143 (0%) | 0 | 5/56 (8.9%) | 5 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Hypothyroidism | 19/153 (12.4%) | 20 | 4/143 (2.8%) | 6 | 7/56 (12.5%) | 7 | 2/8 (25%) | 2 | 0/4 (0%) | 0 |
Eye disorders | ||||||||||
Dry eye | 9/153 (5.9%) | 11 | 3/143 (2.1%) | 4 | 0/56 (0%) | 0 | 1/8 (12.5%) | 2 | 0/4 (0%) | 0 |
Vision blurred | 8/153 (5.2%) | 8 | 2/143 (1.4%) | 2 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gastrointestinal disorders | ||||||||||
Abdominal pain | 34/153 (22.2%) | 56 | 40/143 (28%) | 61 | 8/56 (14.3%) | 12 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Abdominal pain upper | 19/153 (12.4%) | 21 | 11/143 (7.7%) | 14 | 2/56 (3.6%) | 3 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Ascites | 1/153 (0.7%) | 1 | 3/143 (2.1%) | 3 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Constipation | 26/153 (17%) | 30 | 45/143 (31.5%) | 76 | 13/56 (23.2%) | 19 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Diarrhoea | 65/153 (42.5%) | 107 | 88/143 (61.5%) | 203 | 17/56 (30.4%) | 35 | 1/8 (12.5%) | 5 | 0/4 (0%) | 0 |
Dry mouth | 17/153 (11.1%) | 18 | 9/143 (6.3%) | 10 | 3/56 (5.4%) | 4 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Dyspepsia | 9/153 (5.9%) | 10 | 16/143 (11.2%) | 21 | 5/56 (8.9%) | 7 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Haemorrhoids | 2/153 (1.3%) | 2 | 10/143 (7%) | 10 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Nausea | 47/153 (30.7%) | 69 | 85/143 (59.4%) | 283 | 16/56 (28.6%) | 23 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Stomatitis | 10/153 (6.5%) | 11 | 43/143 (30.1%) | 75 | 4/56 (7.1%) | 4 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vomiting | 33/153 (21.6%) | 53 | 53/143 (37.1%) | 84 | 12/56 (21.4%) | 20 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
General disorders | ||||||||||
Asthenia | 19/153 (12.4%) | 32 | 30/143 (21%) | 57 | 5/56 (8.9%) | 8 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Chest pain | 8/153 (5.2%) | 9 | 3/143 (2.1%) | 4 | 4/56 (7.1%) | 5 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Fatigue | 58/153 (37.9%) | 79 | 70/143 (49%) | 177 | 9/56 (16.1%) | 9 | 2/8 (25%) | 2 | 0/4 (0%) | 0 |
Influenza like illness | 14/153 (9.2%) | 20 | 4/143 (2.8%) | 4 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Malaise | 10/153 (6.5%) | 11 | 6/143 (4.2%) | 8 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Mucosal inflammation | 7/153 (4.6%) | 7 | 27/143 (18.9%) | 49 | 2/56 (3.6%) | 2 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Oedema peripheral | 18/153 (11.8%) | 24 | 11/143 (7.7%) | 13 | 10/56 (17.9%) | 11 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Peripheral swelling | 4/153 (2.6%) | 5 | 0/143 (0%) | 0 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pyrexia | 24/153 (15.7%) | 29 | 20/143 (14%) | 28 | 6/56 (10.7%) | 7 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Temperature intolerance | 1/153 (0.7%) | 2 | 8/143 (5.6%) | 12 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Infections and infestations | ||||||||||
Cystitis | 4/153 (2.6%) | 4 | 5/143 (3.5%) | 8 | 4/56 (7.1%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Influenza | 7/153 (4.6%) | 8 | 4/143 (2.8%) | 4 | 1/56 (1.8%) | 1 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Nasopharyngitis | 20/153 (13.1%) | 31 | 10/143 (7%) | 13 | 8/56 (14.3%) | 12 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Oral candidiasis | 3/153 (2%) | 4 | 6/143 (4.2%) | 6 | 4/56 (7.1%) | 5 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Paronychia | 1/153 (0.7%) | 1 | 8/143 (5.6%) | 17 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Tooth infection | 8/153 (5.2%) | 9 | 5/143 (3.5%) | 5 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Upper respiratory tract infection | 16/153 (10.5%) | 17 | 8/143 (5.6%) | 11 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Urinary tract infection | 14/153 (9.2%) | 19 | 15/143 (10.5%) | 23 | 7/56 (12.5%) | 9 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||
Fall | 11/153 (7.2%) | 13 | 5/143 (3.5%) | 5 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Investigations | ||||||||||
Alanine aminotransferase increased | 22/153 (14.4%) | 33 | 16/143 (11.2%) | 30 | 5/56 (8.9%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Aspartate aminotransferase increased | 24/153 (15.7%) | 33 | 12/143 (8.4%) | 24 | 6/56 (10.7%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Blood alkaline phosphatase increased | 22/153 (14.4%) | 30 | 6/143 (4.2%) | 9 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Gamma-glutamyltransferase increased | 8/153 (5.2%) | 8 | 3/143 (2.1%) | 5 | 1/56 (1.8%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neutrophil count decreased | 2/153 (1.3%) | 2 | 32/143 (22.4%) | 64 | 1/56 (1.8%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Platelet count decreased | 2/153 (1.3%) | 4 | 10/143 (7%) | 28 | 2/56 (3.6%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Weight decreased | 7/153 (4.6%) | 7 | 17/143 (11.9%) | 17 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
White blood cell count decreased | 1/153 (0.7%) | 1 | 17/143 (11.9%) | 47 | 1/56 (1.8%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||
Decreased appetite | 36/153 (23.5%) | 49 | 57/143 (39.9%) | 114 | 2/56 (3.6%) | 2 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Dehydration | 11/153 (7.2%) | 11 | 7/143 (4.9%) | 7 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hyperglycaemia | 8/153 (5.2%) | 24 | 4/143 (2.8%) | 4 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypoalbuminaemia | 5/153 (3.3%) | 5 | 8/143 (5.6%) | 17 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hypokalaemia | 13/153 (8.5%) | 25 | 23/143 (16.1%) | 38 | 2/56 (3.6%) | 4 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hyponatraemia | 10/153 (6.5%) | 11 | 6/143 (4.2%) | 7 | 3/56 (5.4%) | 4 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||
Arthralgia | 31/153 (20.3%) | 52 | 10/143 (7%) | 11 | 11/56 (19.6%) | 17 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Back pain | 25/153 (16.3%) | 29 | 24/143 (16.8%) | 27 | 11/56 (19.6%) | 13 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Muscle spasms | 8/153 (5.2%) | 9 | 5/143 (3.5%) | 7 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Muscular weakness | 5/153 (3.3%) | 7 | 1/143 (0.7%) | 1 | 3/56 (5.4%) | 3 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Myalgia | 8/153 (5.2%) | 9 | 12/143 (8.4%) | 15 | 2/56 (3.6%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neck pain | 4/153 (2.6%) | 5 | 5/143 (3.5%) | 5 | 1/56 (1.8%) | 1 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Pain in extremity | 18/153 (11.8%) | 21 | 11/143 (7.7%) | 11 | 6/56 (10.7%) | 7 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Nervous system disorders | ||||||||||
Dizziness | 24/153 (15.7%) | 29 | 27/143 (18.9%) | 54 | 5/56 (8.9%) | 9 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Dysgeusia | 5/153 (3.3%) | 5 | 13/143 (9.1%) | 14 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Headache | 21/153 (13.7%) | 26 | 22/143 (15.4%) | 37 | 16/56 (28.6%) | 25 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Neuropathy peripheral | 1/153 (0.7%) | 1 | 28/143 (19.6%) | 41 | 4/56 (7.1%) | 4 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Paraesthesia | 6/153 (3.9%) | 7 | 8/143 (5.6%) | 10 | 1/56 (1.8%) | 1 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Peripheral sensory neuropathy | 3/153 (2%) | 3 | 31/143 (21.7%) | 51 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Psychiatric disorders | ||||||||||
Anger | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Anxiety | 9/153 (5.9%) | 11 | 4/143 (2.8%) | 6 | 4/56 (7.1%) | 4 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Depression | 7/153 (4.6%) | 7 | 5/143 (3.5%) | 5 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Discouragement | 0/153 (0%) | 0 | 0/143 (0%) | 0 | 0/56 (0%) | 0 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Insomnia | 12/153 (7.8%) | 14 | 10/143 (7%) | 11 | 7/56 (12.5%) | 7 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Renal and urinary disorders | ||||||||||
Proteinuria | 5/153 (3.3%) | 7 | 10/143 (7%) | 27 | 2/56 (3.6%) | 5 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Renal impairment | 1/153 (0.7%) | 1 | 0/143 (0%) | 0 | 1/56 (1.8%) | 1 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||
Cough | 26/153 (17%) | 31 | 23/143 (16.1%) | 26 | 7/56 (12.5%) | 9 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Dysphonia | 2/153 (1.3%) | 2 | 8/143 (5.6%) | 9 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Dyspnoea | 20/153 (13.1%) | 25 | 15/143 (10.5%) | 22 | 6/56 (10.7%) | 8 | 1/8 (12.5%) | 1 | 0/4 (0%) | 0 |
Epistaxis | 2/153 (1.3%) | 3 | 23/143 (16.1%) | 30 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Hiccups | 2/153 (1.3%) | 3 | 8/143 (5.6%) | 10 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Oropharyngeal pain | 4/153 (2.6%) | 4 | 8/143 (5.6%) | 8 | 3/56 (5.4%) | 3 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Productive cough | 8/153 (5.2%) | 8 | 6/143 (4.2%) | 7 | 5/56 (8.9%) | 6 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Rhinorrhoea | 9/153 (5.9%) | 10 | 13/143 (9.1%) | 15 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||
Alopecia | 11/153 (7.2%) | 11 | 29/143 (20.3%) | 32 | 0/56 (0%) | 0 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Dermatitis acneiform | 3/153 (2%) | 6 | 8/143 (5.6%) | 22 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Dry skin | 19/153 (12.4%) | 21 | 14/143 (9.8%) | 15 | 9/56 (16.1%) | 11 | 3/8 (37.5%) | 3 | 1/4 (25%) | 1 |
Palmar-plantar erythrodysaesthesia syndrome | 1/153 (0.7%) | 1 | 25/143 (17.5%) | 35 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Pruritus | 25/153 (16.3%) | 37 | 12/143 (8.4%) | 15 | 14/56 (25%) | 23 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Rash | 19/153 (12.4%) | 27 | 16/143 (11.2%) | 22 | 10/56 (17.9%) | 12 | 2/8 (25%) | 3 | 0/4 (0%) | 0 |
Rash maculo-papular | 8/153 (5.2%) | 9 | 3/143 (2.1%) | 3 | 2/56 (3.6%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Skin hyperpigmentation | 0/153 (0%) | 0 | 8/143 (5.6%) | 10 | 1/56 (1.8%) | 2 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Vascular disorders | ||||||||||
Hypertension | 19/153 (12.4%) | 25 | 16/143 (11.2%) | 23 | 1/56 (1.8%) | 1 | 0/8 (0%) | 0 | 1/4 (25%) | 1 |
Hypotension | 4/153 (2.6%) | 4 | 3/143 (2.1%) | 3 | 5/56 (8.9%) | 5 | 0/8 (0%) | 0 | 0/4 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
Name/Title | Senior Vice President, Global Clinical Development |
---|---|
Organization | Merck Sharp & Dohme LLC |
Phone | 1-800-672-6372 |
ClinicalTrialsDisclosure@merck.com |
- 3475-177
- 2015-002024-89
- 163238
- MK-3475-177
- KEYNOTE-177