A Study of Pembrolizumab (MK-3475) in Participants With Recurrent or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-059/KEYNOTE-059)
Study Details
Study Description
Brief Summary
This is a study of pembrolizumab (MK-3475) for advanced gastric or gastroesophageal junction adenocarcinoma; pembrolizumab will be given as monotherapy to participants who have had previous treatment or who are treatment-naïve; pembrolizumab will also be evaluated as combination therapy with cisplatin and 5-Fluorouracil (5-FU) or (Japan only) capecitabine in treatment-naïve participants. The primary study hypothesis is that pembrolizumab will provide a clinically meaningful Overall Response Rate (ORR).
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 2 |
Detailed Description
This study will have 3 cohorts. In Cohort 1, participants who have received at least two prior therapies for their advanced disease will receive monotherapy with pembrolizumab. In Cohort 2, participants who have not received any previous therapy for their disease will receive pembrolizumab in combination with cisplatin and 5-FU or (Japan only) capecitabine. In Cohort 3, participants who have not received any previous therapy and who have programmed death ligand 1 (PD-L1)-positive tumors will receive pembrolizumab monotherapy.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1: Pembrolizumab monotherapy, previously treated Participants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) |
Biological: pembrolizumab
IV infusion
Other Names:
|
Experimental: Cohort 2: Pembrolizumab combination therapy, treatment naive Participants receive pembrolizumab 200 mg IV each 3-week cycle (Q3W) + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle |
Biological: pembrolizumab
IV infusion
Other Names:
Drug: cisplatin
IV infusion
Other Names:
Drug: 5-FU
IV infusion
Other Names:
Drug: capecitabine
oral tablets
Other Names:
|
Experimental: Cohort 3: Pembrolizumab monotherapy, treatment naive, PD-L1 positive Programmed death-ligand 1 (PD-L1) positive participants receive pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) |
Biological: pembrolizumab
IV infusion
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing Adverse Events (AEs) [Up to approximately 65 months]
An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who experienced at least one AE is presented. Per protocol, the number of participants who experienced at least one AE during first course pembrolizumab treatment is presented.
- Number of Participants Discontinuing Study Drug Due to AEs [Up to approximately 52 months]
An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinued study drug due to an AE is presented. Per protocol, the number of participants who discontinued drug during first course pembrolizumab treatment is presented.
- Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3 [Up to approximately 75 months]
The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of programmed death-ligand 1 [PD-L1] tumor status) in Cohorts 1 and 3 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented.
- Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3 [Up to approximately 75 months]
The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of all participants in Cohorts 1 and 3 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Secondary Outcome Measures
- Objective Response Rate (ORR) For All Participants in Cohort 2 [Up to approximately 75 months]
The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) in Cohort 2 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented.
- Objective Response Rate For PD-L1 Positive Participants in Cohort 2 [Up to approximately 75 months]
The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of participants in Cohort 2 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented.
- Duration of Response (DOR) For All Participants [Up to approximately 75 months]
Duration of Response (DOR) was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD 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. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
- Duration of Response For PD-L1 Positive Participants [Up to approximately 75 months]
DOR was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD 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. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
- Progression-Free Survival (PFS) For All Participants [Up to approximately 75 months]
Progression-Free Survival (PFS) was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
- Progression-Free Survival For PD-L1 Positive Participants [Up to approximately 75 months]
PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
- Overall Survival (OS) For All Participants [Up to approximately 75 months]
Overall Survival (OS) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented.
- Overall Survival For PD-L1 Positive Participants [Up to approximately 75 months]
OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
- Disease Control Rate (DCR) For All Participants [Up to approximately 75 months]
Disease Control Rate (DCR) was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) who had a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented.
- Disease Control Rate For PD-L1 Positive Participants [Up to approximately 75 months]
DCR was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of participants with PD-L1+ tumor status who experienced a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status.
Eligibility Criteria
Criteria
Inclusion Criteria - Cohort 1:
-
Received and progressed on ≥2 prior chemotherapy regimens for their advanced disease; prior regimen must have included a cisplatin and a fluoropyridine
-
Human epidermal growth factor receptor 2 (HER-2/neu) negative, or, if HER2/neu positive, must have previously received treatment with trastuzumab
Inclusion Criteria - Cohort 2 or 3:
-
HER2/neu negative
-
Has not received prior systemic anti-cancer therapy for their advanced carcinoma (systemic therapy received in the neoadjuvant and adjuvant setting does not count)
Inclusion Criteria - All Participants:
-
Histologically- or cytologically-confirmed recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma that is considered incurable by local therapies
-
Willing to provide tissue for PD-L1 biomarker analysis from newly-obtained and/or archival tissue
-
Measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to first dose of study drug
-
Life expectancy of at least 3 months
-
Female participants of childbearing potential should have a negative pregnancy test and be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
-
Male participants should agree to use an adequate method of contraception starting with the first dose through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
-
Adequate organ function
Exclusion Criteria - All Participants:
-
Currently participating and receiving study therapy or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of study drug
-
Active autoimmune disease that has required systemic treatment in past 2 years
-
Immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug
-
Weight loss >10% over 2 months prior to first dose of study drug
-
Clinical evidence of ascites by physical exam
-
Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier
-
Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered from AEs due to a previously administered agent
-
Known additional malignancy that is progressing or requires active treatment excepting basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
-
Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
-
Known history of, or any evidence of active, non-infectious pneumonitis
-
Active infection requiring systemic therapy
-
Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
-
Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study drug (180 days for participants receiving cisplatin + 5FU)
-
Prior therapy with an anti-programmed death-1 (PD-1), anti-PD-L1, or anti-PD-L2 agent
-
Human immunodeficiency virus (HIV)
-
Hepatitis B or C
-
Received live vaccine within 30 days of planned start of study drug
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.- 3475-059
- MK-3475-059
- KEYNOTE-059
- 2014-003574-16
Study Results
Participant Flow
Recruitment Details | Male and female participants of at least 18 years of age with recurrent or metastatic gastric or gastro-esophageal junction (GEJ) adenocarcinoma were enrolled in this study. |
---|---|
Pre-assignment Detail | 318 participants were originally allocated to the study. No study information was collected from 3 participants, who were excluded from all analyses, including disposition. Per protocol, response/progression or adverse events during the second pembrolizumab course were not counted towards efficacy outcome measures or safety outcome measures respectively. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Period Title: Overall Study | |||
STARTED | 259 | 25 | 31 |
Second Course Pembrolizumab | 3 | 1 | 2 |
COMPLETED | 0 | 0 | 0 |
NOT COMPLETED | 259 | 25 | 31 |
Baseline Characteristics
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive | Total |
---|---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Total of all reporting groups |
Overall Participants | 259 | 25 | 31 | 315 |
Age (Years) [Mean (Standard Deviation) ] | ||||
Mean (Standard Deviation) [Years] |
61.0
(11.4)
|
58.8
(16.6)
|
60.3
(11.2)
|
60.7
(11.9)
|
Sex: Female, Male (Count of Participants) | ||||
Female |
61
23.6%
|
9
36%
|
12
38.7%
|
82
26%
|
Male |
198
76.4%
|
16
64%
|
19
61.3%
|
233
74%
|
Ethnicity (NIH/OMB) (Count of Participants) | ||||
Hispanic or Latino |
17
6.6%
|
1
4%
|
3
9.7%
|
21
6.7%
|
Not Hispanic or Latino |
228
88%
|
23
92%
|
28
90.3%
|
279
88.6%
|
Unknown or Not Reported |
14
5.4%
|
1
4%
|
0
0%
|
15
4.8%
|
Race (NIH/OMB) (Count of Participants) | ||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
41
15.8%
|
17
68%
|
15
48.4%
|
73
23.2%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
5
1.9%
|
0
0%
|
0
0%
|
5
1.6%
|
White |
200
77.2%
|
8
32%
|
16
51.6%
|
224
71.1%
|
More than one race |
2
0.8%
|
0
0%
|
0
0%
|
2
0.6%
|
Unknown or Not Reported |
11
4.2%
|
0
0%
|
0
0%
|
11
3.5%
|
Outcome Measures
Title | Number of Participants Experiencing Adverse Events (AEs) |
---|---|
Description | An AE is defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who experienced at least one AE is presented. Per protocol, the number of participants who experienced at least one AE during first course pembrolizumab treatment is presented. |
Time Frame | Up to approximately 65 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 25 | 31 |
Count of Participants [Participants] |
248
95.8%
|
25
100%
|
31
100%
|
Title | Number of Participants Discontinuing Study Drug Due to AEs |
---|---|
Description | An AE was defined as any untoward medical occurrence in a participant administered study drug and which does not necessarily have to have a causal relationship with the study drug. The number of participants who discontinued study drug due to an AE is presented. Per protocol, the number of participants who discontinued drug during first course pembrolizumab treatment is presented. |
Time Frame | Up to approximately 52 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 25 | 31 |
Count of Participants [Participants] |
18
6.9%
|
4
16%
|
0
0%
|
Title | Objective Response Rate (ORR) For All Participants in Cohorts 1 and 3 |
---|---|
Description | The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of programmed death-ligand 1 [PD-L1] tumor status) in Cohorts 1 and 3 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants in Cohorts 1 and 3 who received ≥1 dose of study drug. Per protocol, Cohort 2 was not included in this outcome measure. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 0 | 31 |
Number (95% Confidence Interval) [Percentage of Participants] |
11.6
4.5%
|
22.6
90.4%
|
Title | Objective Response Rate For PD-L1 Positive Participants in Cohorts 1 and 3 |
---|---|
Description | The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of all participants in Cohorts 1 and 3 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants in Cohorts 1 and 3 with a positive PD-L1 tumor status who received ≥1 dose of study drug. Per protocol, Cohort 2 was not included in this outcome measure. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 148 | 0 | 31 |
Number (95% Confidence Interval) [Percentage of Participants] |
15.5
6%
|
22.6
90.4%
|
Title | Objective Response Rate (ORR) For All Participants in Cohort 2 |
---|---|
Description | The Objective Response Rate (ORR) was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) in Cohort 2 who had a CR or PR during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants in Cohort 2 who received ≥1 dose of study drug. Per protocol, Cohorts 1 and 3 were not included in this outcome measure. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 0 | 25 | 0 |
Number (95% Confidence Interval) [Percentage of Participants] |
60.0
23.2%
|
Title | Objective Response Rate For PD-L1 Positive Participants in Cohort 2 |
---|---|
Description | The ORR was defined as the percentage of participants in the analysis population who had a CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, as assessed by central radiology review. The percentage of participants in Cohort 2 with PD-L1+ tumor status who experienced a CR or PR during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants in Cohort 2 with a positive PD-L1 tumor status who received ≥1 dose of study drug. Per protocol, Cohorts 1 and 3 were not included in this outcome measure. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 0 | 15 | 0 |
Number (95% Confidence Interval) [Percentage of Participants] |
73.3
28.3%
|
Title | Duration of Response (DOR) For All Participants |
---|---|
Description | Duration of Response (DOR) was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD 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. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug and demonstrated a confirmed response (CR or PR). |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 30 | 15 | 7 |
Median (Full Range) [Months] |
16.1
|
4.6
|
38.0
|
Title | Duration of Response For PD-L1 Positive Participants |
---|---|
Description | DOR was defined as the time from first documented evidence of CR or PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, based on central imaging vendor assessment, until disease progression (PD) or death, whichever occurred first. PD 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. The appearance of one or more new lesions is also considered PD. Participants who had not progressed or died at the time of analysis were censored at the date of their last tumor assessment. The DOR for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants with a positive PD-L1 tumor status who received ≥1 dose of study drug and demonstrated a confirmed response (CR or PR). |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 23 | 11 | 7 |
Median (Full Range) [Months] |
NA
|
4.6
|
38.0
|
Title | Progression-Free Survival (PFS) For All Participants |
---|---|
Description | Progression-Free Survival (PFS) was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 25 | 31 |
Median (95% Confidence Interval) [Months] |
2.0
|
6.6
|
2.9
|
Title | Progression-Free Survival For PD-L1 Positive Participants |
---|---|
Description | PFS was defined as the time from randomization to the first documented disease progression, or death due to any cause, whichever occurred first. Per RECIST 1.1, progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. The PFS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants with a positive PD-L1 tumor status who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 148 | 15 | 31 |
Median (95% Confidence Interval) [Months] |
2.1
|
6.5
|
2.9
|
Title | Overall Survival (OS) For All Participants |
---|---|
Description | Overall Survival (OS) was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for all participants (regardless of PD-L1 tumor status) during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 25 | 31 |
Median (95% Confidence Interval) [Months] |
5.5
|
13.8
|
20.7
|
Title | Overall Survival For PD-L1 Positive Participants |
---|---|
Description | OS was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. The OS for only PD-L1 positive participants during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants with a positive PD-L1 tumor status who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 148 | 15 | 31 |
Median (95% Confidence Interval) [Months] |
5.8
|
11.1
|
20.7
|
Title | Disease Control Rate (DCR) For All Participants |
---|---|
Description | Disease Control Rate (DCR) was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of all participants (regardless of PD-L1 tumor status) who had a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 259 | 25 | 31 |
Number (95% Confidence Interval) [Percentage of Participants] |
27.0
10.4%
|
80.0
320%
|
32.3
104.2%
|
Title | Disease Control Rate For PD-L1 Positive Participants |
---|---|
Description | DCR was defined as the percentage of participants in the analysis population who had a CR or a PR (CR: Disappearance of all target lesions; PR: At least a 30% decrease in the sum of diameters of target lesions) or stable disease (SD); (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease) for ≥6 months, (for Cohort 1 ≥2 months) as assessed by central radiology review. The percentage of participants with PD-L1+ tumor status who experienced a CR or PR or SD during first course pembrolizumab treatment per protocol, is presented. Note: All participants in Cohort 3 had a PD-L1-positive tumor status. |
Time Frame | Up to approximately 75 months |
Outcome Measure Data
Analysis Population Description |
---|
All enrolled participants with a positive PD-L1 tumor status who received ≥1 dose of study drug. |
Arm/Group Title | Cohort 1: Pembrolizumab Monotherapy, Previously Treated | Cohort 2: Pembrolizumab Combination Therapy, Treatment Naive | Cohort 3: Pembrolizumab Monotherapy, Treatment Naive, PD-L1 Positive |
---|---|---|---|
Arm/Group Description | Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Participants received pembrolizumab 200 mg IV each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-Fluorouracil (5-FU) 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, twice per day (BID) on Days 1-14 of each 3-week cycle. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. | Programmed death-ligand 1 (PD-L1) positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. Eligible participants allocated to the pembrolizumab first course, who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg of each 3 week cycle for up to 17 cycles up to approximately an additional year. |
Measure Participants | 148 | 15 | 31 |
Number (95% Confidence Interval) [Percentage of Participants] |
33.1
12.8%
|
80.0
320%
|
32.3
104.2%
|
Adverse Events
Time Frame | Up to approximately 75 months | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | The population analyzed for all-cause mortality consisted of all allocated participants. The population for AEs consisted of all allocated participants who received ≥1 dose of study drug. Per protocol disease progression of cancer was not considered an AE unless related to study drug. Therefore the following AE preferred terms not related to the drug were excluded: Neoplasm progression, Malignant neoplasm progression and Disease progression. | |||||||||||
Arm/Group Title | Cohort 1 First Course | Cohort 2 First Course | Cohort 3 First Course | Cohort 1 Second Course | Cohort 2 Second Course | Cohort 3 Second Course | ||||||
Arm/Group Description | Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months. | Participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 40 months + cisplatin 80 mg/m^2 IV Q3W for up to 6 cycles + 5-FU 800 mg/m^2 IV on Days 1-5 every 3 weeks or (Japan only) capecitabine 1000 mg/m^2 orally, BID on Days 1-14 of each 3-week cycle. | PD-L1 positive participants received pembrolizumab 200 mg IV on Day 1 of each 3-week cycle (Q3W) for up to 52 months | Eligible participants allocated to the pembrolizumab first course in Cohort 1 who stopped pembrolizumab with stable disease (SD) or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg on Day 1 of each 3 week cycle (Q3W) for up to 17 cycles up to approximately an additional year. | Eligible participants allocated to the pembrolizumab first course in Cohort 2 who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg on Day 1 of each 3 week cycle (Q3W) for up to 17 cycles up to approximately an additional year. | Eligible participants allocated to the pembrolizumab first course in Cohort 3 who stopped pembrolizumab with SD or better, initiated a second course of pembrolizumab at the investigator's discretion at 200 mg on Day 1 of each 3 week cycle (Q3W) for up to 17 cycles up to approximately an additional year. | ||||||
All Cause Mortality |
||||||||||||
Cohort 1 First Course | Cohort 2 First Course | Cohort 3 First Course | Cohort 1 Second Course | Cohort 2 Second Course | Cohort 3 Second Course | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 244/259 (94.2%) | 21/25 (84%) | 26/31 (83.9%) | 1/3 (33.3%) | 1/1 (100%) | 1/2 (50%) | ||||||
Serious Adverse Events |
||||||||||||
Cohort 1 First Course | Cohort 2 First Course | Cohort 3 First Course | Cohort 1 Second Course | Cohort 2 Second Course | Cohort 3 Second Course | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 119/259 (45.9%) | 11/25 (44%) | 15/31 (48.4%) | 0/3 (0%) | 0/1 (0%) | 0/2 (0%) | ||||||
Blood and lymphatic system disorders | ||||||||||||
Abdominal lymphadenopathy | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Anaemia | 6/259 (2.3%) | 6 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cardiac disorders | ||||||||||||
Atrial fibrillation | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cardiac arrest | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cardiac tamponade | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Myocardial infarction | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pericardial effusion | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Supraventricular tachycardia | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Congenital, familial and genetic disorders | ||||||||||||
Tracheo-oesophageal fistula | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Endocrine disorders | ||||||||||||
Hypothyroidism | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Thyroiditis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Eye disorders | ||||||||||||
Diffuse uveal melanocytic proliferation | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||
Abdominal pain | 4/259 (1.5%) | 4 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Abdominal pain upper | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Ascites | 2/259 (0.8%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Colitis | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Constipation | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Diarrhoea | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Diverticulum intestinal haemorrhagic | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dysphagia | 7/259 (2.7%) | 7 | 1/25 (4%) | 1 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Enterocolitis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastric haemorrhage | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastric perforation | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastric stenosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastrointestinal haemorrhage | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Haematemesis | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Ileus | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Intestinal obstruction | 6/259 (2.3%) | 6 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Jejunal perforation | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Large intestinal obstruction | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Melaena | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Nausea | 5/259 (1.9%) | 7 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Obstruction gastric | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oesophageal intramural haematoma | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oesophageal perforation | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oesophageal stenosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oesophageal ulcer | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Small intestinal obstruction | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Stomatitis | 0/259 (0%) | 0 | 4/25 (16%) | 4 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Upper gastrointestinal haemorrhage | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vomiting | 5/259 (1.9%) | 6 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
General disorders | ||||||||||||
Asthenia | 4/259 (1.5%) | 4 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Chest pain | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Death | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Fatigue | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastrointestinal complication associated with device | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Influenza like illness | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Multiple organ dysfunction syndrome | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Non-cardiac chest pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pyrexia | 3/259 (1.2%) | 3 | 1/25 (4%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Systemic inflammatory response syndrome | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatobiliary disorders | ||||||||||||
Bile duct stenosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Biliary obstruction | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cholangitis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cholecystitis acute | 1/259 (0.4%) | 1 | 1/25 (4%) | 1 | 1/31 (3.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatic failure | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatic function abnormal | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatic haematoma | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatic pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hepatitis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Jaundice | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Portal vein thrombosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Infections and infestations | ||||||||||||
Abdominal abscess | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Bacteraemia | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Clostridium difficile infection | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Disseminated varicella zoster virus infection | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Diverticulitis intestinal haemorrhagic | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Encephalitis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Liver abscess | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Osteomyelitis | 1/259 (0.4%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pharyngitis | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumocystis jirovecii pneumonia | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumonia | 4/259 (1.5%) | 6 | 0/25 (0%) | 0 | 2/31 (6.5%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pyelonephritis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Sepsis | 5/259 (1.9%) | 5 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Septic shock | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Staphylococcal bacteraemia | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Subdiaphragmatic abscess | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Urinary tract infection | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Wound infection | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||||||||
Anastomotic stenosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Post procedural haemorrhage | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Rib fracture | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Thoracic vertebral fracture | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vascular pseudoaneurysm | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Investigations | ||||||||||||
Alanine aminotransferase increased | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Aspartate aminotransferase increased | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Blood bilirubin increased | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Blood creatine phosphokinase increased | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Blood creatinine increased | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Transaminases increased | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Urine output decreased | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||
Decreased appetite | 1/259 (0.4%) | 1 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dehydration | 4/259 (1.5%) | 4 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Failure to thrive | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypercalcaemia | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hyperglycaemia | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hyponatraemia | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||
Arthralgia | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Back pain | 5/259 (1.9%) | 5 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Musculoskeletal chest pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Musculoskeletal pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Myositis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Neck pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pain in extremity | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Polymyalgia rheumatica | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
Cancer pain | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Metastases to adrenals | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oesophageal squamous cell carcinoma | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Renal cancer | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Squamous cell carcinoma of skin | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Tumour pain | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Nervous system disorders | ||||||||||||
Altered state of consciousness | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cauda equina syndrome | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Cerebrovascular accident | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dizziness | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dysarthria | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Seizure | 1/259 (0.4%) | 1 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Syncope | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Transient ischaemic attack | 1/259 (0.4%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Unresponsive to stimuli | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vertebral artery occlusion | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Psychiatric disorders | ||||||||||||
Anxiety | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Confusional state | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Delirium | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Depression | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Drug dependence | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Renal and urinary disorders | ||||||||||||
Acute kidney injury | 6/259 (2.3%) | 6 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Chronic kidney disease | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hydronephrosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Nephrotic syndrome | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Dyspnoea | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypoxia | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pleural effusion | 9/259 (3.5%) | 9 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumonia aspiration | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumonitis | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pulmonary embolism | 6/259 (2.3%) | 6 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Respiratory failure | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||
Lichen planus | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Palmar-plantar erythrodysaesthesia syndrome | 0/259 (0%) | 0 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Rash maculo-papular | 0/259 (0%) | 0 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vascular disorders | ||||||||||||
Deep vein thrombosis | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Embolism | 1/259 (0.4%) | 1 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Haematoma | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Internal haemorrhage | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vena cava thrombosis | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||
Cohort 1 First Course | Cohort 2 First Course | Cohort 3 First Course | Cohort 1 Second Course | Cohort 2 Second Course | Cohort 3 Second Course | |||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 237/259 (91.5%) | 25/25 (100%) | 31/31 (100%) | 0/3 (0%) | 0/1 (0%) | 0/2 (0%) | ||||||
Blood and lymphatic system disorders | ||||||||||||
Anaemia | 58/259 (22.4%) | 69 | 11/25 (44%) | 13 | 7/31 (22.6%) | 9 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Leukopenia | 4/259 (1.5%) | 7 | 2/25 (8%) | 3 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Neutropenia | 3/259 (1.2%) | 3 | 9/25 (36%) | 12 | 1/31 (3.2%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Thrombocytopenia | 8/259 (3.1%) | 10 | 3/25 (12%) | 5 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Ear and labyrinth disorders | ||||||||||||
Tinnitus | 0/259 (0%) | 0 | 4/25 (16%) | 4 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Endocrine disorders | ||||||||||||
Hyperthyroidism | 10/259 (3.9%) | 10 | 4/25 (16%) | 4 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypothyroidism | 24/259 (9.3%) | 24 | 2/25 (8%) | 2 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastrointestinal disorders | ||||||||||||
Abdominal discomfort | 2/259 (0.8%) | 2 | 2/25 (8%) | 2 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Abdominal distension | 15/259 (5.8%) | 15 | 2/25 (8%) | 2 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Abdominal pain | 49/259 (18.9%) | 56 | 3/25 (12%) | 3 | 8/31 (25.8%) | 13 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Abdominal pain upper | 19/259 (7.3%) | 25 | 4/25 (16%) | 8 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Ascites | 16/259 (6.2%) | 18 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Constipation | 52/259 (20.1%) | 57 | 14/25 (56%) | 22 | 7/31 (22.6%) | 7 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Diarrhoea | 46/259 (17.8%) | 55 | 14/25 (56%) | 18 | 8/31 (25.8%) | 13 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dry mouth | 8/259 (3.1%) | 8 | 2/25 (8%) | 4 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dyspepsia | 9/259 (3.5%) | 9 | 2/25 (8%) | 3 | 3/31 (9.7%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dysphagia | 31/259 (12%) | 36 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gastrooesophageal reflux disease | 10/259 (3.9%) | 12 | 2/25 (8%) | 4 | 2/31 (6.5%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Nausea | 65/259 (25.1%) | 74 | 15/25 (60%) | 22 | 8/31 (25.8%) | 10 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Stomatitis | 10/259 (3.9%) | 10 | 17/25 (68%) | 29 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vomiting | 36/259 (13.9%) | 44 | 10/25 (40%) | 23 | 6/31 (19.4%) | 12 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
General disorders | ||||||||||||
Asthenia | 24/259 (9.3%) | 26 | 4/25 (16%) | 7 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Chest discomfort | 2/259 (0.8%) | 2 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Fatigue | 93/259 (35.9%) | 105 | 10/25 (40%) | 13 | 10/31 (32.3%) | 10 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Generalised oedema | 0/259 (0%) | 0 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Influenza like illness | 4/259 (1.5%) | 5 | 0/25 (0%) | 0 | 4/31 (12.9%) | 5 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Malaise | 7/259 (2.7%) | 7 | 5/25 (20%) | 14 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Mucosal inflammation | 1/259 (0.4%) | 1 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oedema | 9/259 (3.5%) | 9 | 4/25 (16%) | 10 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oedema peripheral | 43/259 (16.6%) | 57 | 1/25 (4%) | 1 | 4/31 (12.9%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pyrexia | 25/259 (9.7%) | 35 | 6/25 (24%) | 9 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Infections and infestations | ||||||||||||
Nasopharyngitis | 7/259 (2.7%) | 8 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumonia | 8/259 (3.1%) | 10 | 2/25 (8%) | 3 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Investigations | ||||||||||||
Alanine aminotransferase increased | 14/259 (5.4%) | 19 | 2/25 (8%) | 3 | 2/31 (6.5%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Aspartate aminotransferase increased | 30/259 (11.6%) | 34 | 2/25 (8%) | 2 | 4/31 (12.9%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Blood alkaline phosphatase increased | 31/259 (12%) | 32 | 1/25 (4%) | 1 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Blood creatinine increased | 13/259 (5%) | 15 | 5/25 (20%) | 6 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Gamma-glutamyltransferase increased | 7/259 (2.7%) | 9 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Haemoglobin decreased | 4/259 (1.5%) | 4 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Lymphocyte count decreased | 6/259 (2.3%) | 8 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Neutrophil count decreased | 2/259 (0.8%) | 3 | 13/25 (52%) | 30 | 1/31 (3.2%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Platelet count decreased | 3/259 (1.2%) | 4 | 5/25 (20%) | 7 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Weight decreased | 38/259 (14.7%) | 41 | 5/25 (20%) | 6 | 4/31 (12.9%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Weight increased | 2/259 (0.8%) | 2 | 3/25 (12%) | 13 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
White blood cell count decreased | 2/259 (0.8%) | 2 | 4/25 (16%) | 9 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Metabolism and nutrition disorders | ||||||||||||
Decreased appetite | 73/259 (28.2%) | 81 | 13/25 (52%) | 22 | 11/31 (35.5%) | 14 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dehydration | 15/259 (5.8%) | 20 | 2/25 (8%) | 2 | 2/31 (6.5%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Diabetes mellitus | 0/259 (0%) | 0 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hyperglycaemia | 23/259 (8.9%) | 29 | 3/25 (12%) | 6 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypoalbuminaemia | 24/259 (9.3%) | 24 | 1/25 (4%) | 1 | 4/31 (12.9%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypokalaemia | 12/259 (4.6%) | 13 | 3/25 (12%) | 3 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypomagnesaemia | 2/259 (0.8%) | 2 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hyponatraemia | 23/259 (8.9%) | 26 | 1/25 (4%) | 2 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypophosphataemia | 10/259 (3.9%) | 14 | 2/25 (8%) | 4 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||||||||
Arthralgia | 36/259 (13.9%) | 58 | 3/25 (12%) | 3 | 5/31 (16.1%) | 8 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Back pain | 34/259 (13.1%) | 38 | 2/25 (8%) | 2 | 6/31 (19.4%) | 7 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Flank pain | 5/259 (1.9%) | 5 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Groin pain | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Muscular weakness | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Myalgia | 8/259 (3.1%) | 10 | 2/25 (8%) | 2 | 5/31 (16.1%) | 7 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pain in extremity | 9/259 (3.5%) | 12 | 0/25 (0%) | 0 | 5/31 (16.1%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Nervous system disorders | ||||||||||||
Dizziness | 17/259 (6.6%) | 17 | 4/25 (16%) | 5 | 4/31 (12.9%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dysgeusia | 6/259 (2.3%) | 6 | 6/25 (24%) | 9 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Headache | 12/259 (4.6%) | 13 | 5/25 (20%) | 5 | 3/31 (9.7%) | 6 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Neuropathy peripheral | 3/259 (1.2%) | 3 | 3/25 (12%) | 3 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Peripheral sensory neuropathy | 5/259 (1.9%) | 5 | 6/25 (24%) | 7 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Syncope | 2/259 (0.8%) | 3 | 2/25 (8%) | 3 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Psychiatric disorders | ||||||||||||
Anxiety | 15/259 (5.8%) | 18 | 0/25 (0%) | 0 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Insomnia | 17/259 (6.6%) | 20 | 9/25 (36%) | 9 | 2/31 (6.5%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||||||||
Cough | 44/259 (17%) | 50 | 2/25 (8%) | 2 | 6/31 (19.4%) | 8 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dyspnoea | 40/259 (15.4%) | 43 | 1/25 (4%) | 2 | 5/31 (16.1%) | 7 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Epistaxis | 3/259 (1.2%) | 3 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hiccups | 4/259 (1.5%) | 4 | 8/25 (32%) | 16 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Oropharyngeal pain | 8/259 (3.1%) | 8 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pleural effusion | 11/259 (4.2%) | 14 | 2/25 (8%) | 2 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pneumonitis | 2/259 (0.8%) | 2 | 1/25 (4%) | 1 | 3/31 (9.7%) | 4 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||||||||
Alopecia | 3/259 (1.2%) | 3 | 4/25 (16%) | 4 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Dry skin | 17/259 (6.6%) | 18 | 2/25 (8%) | 2 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Palmar-plantar erythrodysaesthesia syndrome | 1/259 (0.4%) | 1 | 3/25 (12%) | 3 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Pruritus | 33/259 (12.7%) | 39 | 4/25 (16%) | 7 | 8/31 (25.8%) | 10 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Rash | 31/259 (12%) | 33 | 2/25 (8%) | 2 | 3/31 (9.7%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Rash maculo-papular | 5/259 (1.9%) | 5 | 1/25 (4%) | 1 | 2/31 (6.5%) | 3 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Skin hyperpigmentation | 1/259 (0.4%) | 1 | 2/25 (8%) | 2 | 1/31 (3.2%) | 1 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Skin lesion | 3/259 (1.2%) | 3 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Urticaria | 1/259 (0.4%) | 1 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vascular disorders | ||||||||||||
Hypertension | 14/259 (5.4%) | 20 | 1/25 (4%) | 1 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Hypotension | 10/259 (3.9%) | 12 | 0/25 (0%) | 0 | 2/31 (6.5%) | 2 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (0%) | 0 |
Vasculitis | 0/259 (0%) | 0 | 2/25 (8%) | 2 | 0/31 (0%) | 0 | 0/3 (0%) | 0 | 0/1 (0%) | 0 | 0/2 (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.
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 |
- 3475-059
- MK-3475-059
- KEYNOTE-059
- 2014-003574-16