Gastric Adenocarcinoma
Conditions
Keywords
Gastric carcinoma, Gastric cancer, Gastroesophageal junction cancer, Gastroesophageal junction carcinoma, Programmed Cell Death-1 (PD1, PD-1),, Programmed Death-Ligand 1 (PDL1, PD-L1), Programmed Cell Death Receptor Ligand 2 (PDL2, PD-L2)
Brief summary
This is a study of pembrolizumab (MK-3475) as first-line treatment for participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Participants whose tumors express programmed death-ligand 1 (PD-L1) will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy \[pembro mono\], pembrolizumab plus standard of care (SOC) chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine \[pembro combo\], or placebo plus SOC chemotherapy with cisplatin plus 5-fluorouracil (5-FU) or capecitabine \[SOC\]. The primary study hypotheses are that pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with PD-L1 Combined Positive Score (CPS) ≥1, pembrolizumab in combination with SOC chemotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10, pembrolizumab monotherapy is non-inferior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1, and pembrolizumab monotherapy is superior to SOC chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.
Detailed description
As specified by the protocol, primary and secondary efficacy analyses will be evaluated in gastric cancer participants with PD-L1 CPS ≥1 (all participants) and PD-L1 CPS ≥10 (OS) by comparing the pembro mono arm or pembro combo arm separately to the SOC arm.
Interventions
BIOLOGICALPembrolizumab
Pembrolizumab 200 mg IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).
DRUGCisplatin
Cisplatin 80 mg/m\^2 IV on Day 1 of each week in 3-week cycles (6 cycle maximum per local country guidelines).
DRUG5-FU
5-FU 800 mg/m\^2/day IV continuous from Day 1-5 of each 3-week cycle.
DRUGCapecitabine
Capecitabine 1000 mg/m\^2 twice daily by oral tablet on Day 1-14 of each 3-week cycle.
DRUGPlacebo
Normal saline IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This study is partially blinded. The participant, study site personnel, and the sponsor will be blinded in the pembrolizumab plus SOC chemotherapy (pembro combo) arm and the placebo plus SOC chemotherapy (SOC) arm, but not in the pembro monotherapy (mono arm) since only one type of study medication will be administered.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to first dose of study medication * Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma * Human epidermal growth factor receptor 2- (HER2/neu-) negative and programmed cell death ligand 1 (PD-L1)-positive * Has measurable disease * Female participants of childbearing potential must be willing to use adequate contraception or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication * Male participants of childbearing potential should agree to use an adequate method of contraception starting with the first dose of study medication through 120 days after the last dose of study medication * Adequate organ function
Exclusion criteria
* Squamous cell or undifferentiated gastric cancer * Previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participant may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization * Major surgery, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of study treatment. * Radiotherapy within 14 days of randomization * Known additional malignancy that is progressing or requires active treatment with the exception of basal cell carcinoma of the skin, 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 * Active autoimmune disease that has required systemic treatment in past 2 years * Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * History of non-infectious pneumonitis that required steroids or current pneumonitis * Active infection requiring systemic therapy * Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of study medication * Prior therapy with an anti-programmed cell death (PD)-1, anti-PD-L1, or anti-PD-L2 agent * Known history of human immunodeficiency virus (HIV) * Known active Hepatitis B or C * Currently participating in and receiving study therapy or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study medication * Received a live vaccine within 30 days prior to the first dose of study medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 36 months | PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred 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. Per protocol, PFS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record. |
| Pembro Combo vs SOC: Overall Survival (OS) in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 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. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record. |
| Pembro Combo vs SOC: OS in Participants With PD-L1 CPS ≥10 | Up to approximately 42 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. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro mono arm and SOC arm and is presented later in the record. |
| Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 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. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record. |
| Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥10 | Up to approximately 42 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. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro combo arm and SOC arm and is presented earlier in the record. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pembro Mono vs SOC: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | Baseline, Week 18 | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and SOC arm and is presented later in the record. |
| Pembro Combo vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-STO22 Pain Symptom Subscale Score | Baseline, Week 18 | EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro mono arm and SOC arm and is presented earlier in the record. |
| Pembro Combo vs SOC: Change From Baseline to Week 18 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | Baseline, Week 18 | The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and SOC arm and is presented earlier in the record. |
| Pembro Combo vs SOC: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 months | ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record. |
| Number of Participants Experiencing an Adverse Event (AE) | Up to approximately 33 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an adverse event. The number of participants who experienced an AE was reported for each arm according to the treatment received. |
| Number of Participants Discontinuing Study Treatment Due to an AE | Up to approximately 30 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an adverse event. The number of participants who discontinued study treatment due to an AE was reported for each arm according to the treatment received. |
| Pembro Mono vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-Module for Gastric Cancer (STO22) Pain Symptom Subscale Score | Baseline, Week 18 | EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro combo arm and SOC arm and is presented later in the record. |
| Pembro Combo vs SOC: Duration of Response (DOR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 months | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 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. DOR is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro mono arm and SOC arm and is presented later in the record. |
| Pembro Mono vs SOC: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 months | ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record. |
| Pembro Mono vs SOC: DOR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 months | For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 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. DOR is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro combo arm and SOC arm and is presented earlier in the record. |
| Pembro Mono vs SOC: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | Up to approximately 42 months | PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred 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. Per protocol, PFS in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record. |
Participant flow
Recruitment details
Participants with advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma who were programmed death-ligand 1 (PD-L1)-positive (Combined Positive Score \[CPS\]≥1) and human epidermal growth factor receptor 2 (HER2/neu)-negative were recruited to the study.
Pre-assignment details
Of 1,787 screened, 763 were randomized 1:1:1 to the pembrolizumab monotherapy (pembro mono) arm, pembrolizumab plus standard of care (SOC) chemotherapy (pembro combo) arm, or placebo plus SOC chemotherapy (SOC) arm. Per protocol, response/progression or adverse events (AEs) that occurred during the second course were not counted towards efficacy outcome measures or safety outcome measures, respectively.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W). Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 256 |
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) Participants received pembrolizumab 200 mg Q3W plus cisplatin 80 mg/m\^2 Q3W plus 5-fluorouracil (5-FU) 800 mg/m\^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m\^2 twice a day (BID) on Days 1-14 Q3W could be substituted for 5-FU per local guidelines. Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion. | 257 |
| Placebo + SOC Chemotherapy (SOC) Participants received placebo IV Q3W plus cisplatin 80 mg/m\^2 Q3W plus 5-FU 800 mg/m\^2/day IV infusion on Days 1-5 Q3W. Capecitabine 1000 mg/m\^2 BID on Days 1-14 Q3W could be substituted for 5-FU per local guidelines. | 250 |
| Total | 763 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 224 | 214 | 225 |
| Overall Study | Did Not Continue on Extension Study | 8 | 10 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 0 |
| Overall Study | Screen Failure | 0 | 1 | 0 |
| Overall Study | Transferred to Extension Study | 15 | 15 | 6 |
| Overall Study | Withdrawal by Subject | 7 | 15 | 15 |
Baseline characteristics
| Characteristic | Pembrolizumab Monotherapy (Pembro Mono) | Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Placebo + SOC Chemotherapy (SOC) | Total |
|---|---|---|---|---|
| Age, Continuous | 59.9 Years STANDARD_DEVIATION 11.6 | 60.9 Years STANDARD_DEVIATION 11.6 | 60.7 Years STANDARD_DEVIATION 12.7 | 60.5 Years STANDARD_DEVIATION 12 |
| Disease Status Locally advanced | 10 Participants | 12 Participants | 13 Participants | 35 Participants |
| Disease Status Metastatic | 245 Participants | 243 Participants | 235 Participants | 723 Participants |
| Disease Status Missing | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 45 Participants | 54 Participants | 46 Participants | 145 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 206 Participants | 196 Participants | 197 Participants | 599 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants | 7 Participants | 7 Participants | 19 Participants |
| Fluoropyrimidine Treatment 5-FU | 97 Participants | 98 Participants | 95 Participants | 290 Participants |
| Fluoropyrimidine Treatment Capecitabine | 159 Participants | 159 Participants | 155 Participants | 473 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 9 Participants | 7 Participants | 13 Participants | 29 Participants |
| Race (NIH/OMB) Asian | 69 Participants | 71 Participants | 67 Participants | 207 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 5 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 9 Participants | 6 Participants | 7 Participants | 22 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) White | 164 Participants | 167 Participants | 154 Participants | 485 Participants |
| Region of Enrollment Asia | 62 Participants | 64 Participants | 61 Participants | 187 Participants |
| Region of Enrollment Europe/North America/Australia | 148 Participants | 148 Participants | 147 Participants | 443 Participants |
| Region of Enrollment Rest of the World | 46 Participants | 45 Participants | 42 Participants | 133 Participants |
| Sex: Female, Male Female | 76 Participants | 62 Participants | 71 Participants | 209 Participants |
| Sex: Female, Male Male | 180 Participants | 195 Participants | 179 Participants | 554 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 229 / 256 | 232 / 257 | 240 / 250 | 2 / 4 | 1 / 5 |
| other Total, other adverse events | 216 / 254 | 239 / 250 | 234 / 244 | 3 / 4 | 5 / 5 |
| serious Total, serious adverse events | 93 / 254 | 122 / 250 | 117 / 244 | 1 / 4 | 0 / 5 |
Outcome results
Primary
Pembro Combo vs SOC: OS in Participants With PD-L1 CPS ≥10
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. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro mono arm and SOC arm and is presented later in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥10 participants in the ITT population randomized to the pembro combo arm and SOC arm were analyzed. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: OS in Participants With PD-L1 CPS ≥10 | 12.3 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: OS in Participants With PD-L1 CPS ≥10 | 10.8 Months |
Comparison: OS in CPS ≥10 participants of the pembro combo arm was compared to OS in CPS ≥10 participants of the SOC arm to address the third primary hypothesis (superiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and Fluoropyrimidine treatment.p-value: 0.1580495% CI: [0.62, 1.17]Regression, Cox
Primary
Pembro Combo vs SOC: Overall Survival (OS) in Participants With PD-L1 CPS ≥1 (All Participants)
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. Per protocol, OS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro combo arm and SOC arm were analyzed. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: Overall Survival (OS) in Participants With PD-L1 CPS ≥1 (All Participants) | 12.5 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: Overall Survival (OS) in Participants With PD-L1 CPS ≥1 (All Participants) | 11.1 Months |
Comparison: OS in CPS ≥1 participants of the pembro combo arm was compared to OS in CPS ≥1 participants of the SOC arm to address the second primary hypothesis (superiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and Fluoropyrimidine treatment.p-value: 0.0461195% CI: [0.7, 1.03]Regression, Cox
Primary
Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants)
PFS was defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred 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. Per protocol, PFS in the pembro combo arm was compared to the SOC arm as a pre-specified primary analysis of the Intent-To-Treat (ITT) population. PFS is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.
Time frame: Up to approximately 36 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro combo arm and SOC arm were analyzed. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants) | 6.9 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: Progression Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Review (BICR) in Participants With PD-L1 CPS ≥1 (All Participants) | 6.4 Months |
Comparison: PFS in CPS ≥1 participants of the pembro combo arm was compared to PFS in CPS ≥1 participants of the SOC arm to address the first primary hypothesis (superiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and fluoropyrimidine treatment.p-value: 0.0391895% CI: [0.7, 1.02]Regression, Cox
Primary
Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥10
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. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥10. Per protocol, OS was compared separately between CPS ≥10 participants of the pembro combo arm and SOC arm and is presented earlier in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥10 participants in the ITT population randomized to the pembro mono arm and SOC arm were analyzed. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥10 | 17.4 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥10 | 10.8 Months |
Comparison: OS in CPS ≥10 participants of the pembro mono arm was compared to OS in CPS ≥10 participants of the SOC arm to address the sixth primary hypothesis (superiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and Fluoropyrimidine treatment.p-value: 0.0149195% CI: [0.49, 0.97]Regression, Cox
Primary
Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥1 (All Participants)
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. Per protocol, OS in the pembro mono arm was compared to the SOC arm as a pre-specified primary analysis of the ITT population. OS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, OS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro mono arm and SOC arm were analyzed. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥1 (All Participants) | 10.6 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: OS in Participants With PD-L1 CPS ≥1 (All Participants) | 11.1 Months |
Comparison: OS in CPS ≥1 participants of the pembro mono arm was compared to OS in CPS ≥1 participants of the SOC arm to address the fourth primary hypothesis (non-inferiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and Fluoropyrimidine treatment.99.2% CI: [0.69, 1.18]
Comparison: OS in CPS ≥1 participants of the pembro mono arm was compared to OS in CPS ≥1 participants of the SOC arm to address the fifth primary hypothesis (superiority to SOC). The comparison was based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and Fluoropyrimidine treatment.p-value: 0.1620595% CI: [0.74, 1.1]Regression, Cox
Secondary
Number of Participants Discontinuing Study Treatment Due to an AE
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an adverse event. The number of participants who discontinued study treatment due to an AE was reported for each arm according to the treatment received.
Time frame: Up to approximately 30 months
Population: All randomized participants who received at least 1 dose of trial treatment were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Number of Participants Discontinuing Study Treatment Due to an AE | 29 Participants |
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Number of Participants Discontinuing Study Treatment Due to an AE | 85 Participants |
| Placebo + SOC Chemotherapy (SOC) | Number of Participants Discontinuing Study Treatment Due to an AE | 58 Participants |
Secondary
Number of Participants Experiencing an Adverse Event (AE)
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an adverse event. The number of participants who experienced an AE was reported for each arm according to the treatment received.
Time frame: Up to approximately 33 months
Population: All randomized participants who received at least 1 dose of trial treatment were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Number of Participants Experiencing an Adverse Event (AE) | 242 Participants |
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Number of Participants Experiencing an Adverse Event (AE) | 244 Participants |
| Placebo + SOC Chemotherapy (SOC) | Number of Participants Experiencing an Adverse Event (AE) | 240 Participants |
Secondary
Pembro Combo vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-STO22 Pain Symptom Subscale Score
EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro mono arm and SOC arm and is presented earlier in the record.
Time frame: Baseline, Week 18
Population: Participants in the pembro combo arm and SOC arm who received ≥1 dose of study drug and who had EORTC-QLQ-STO22 assessments available at baseline or post-baseline up to Week 18. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-STO22 Pain Symptom Subscale Score | -10.12 Score on a Scale |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-STO22 Pain Symptom Subscale Score | -3.56 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-STO22 Pain symptom subscale score was compared between all participants of the pembro combo arm and the SOC arm. Comparison based on cLDA model with GHS/QoL score as response variable and treatment by visit interaction and stratification factors (geographic region, disease status, and fluoropyrimidine treatment) as covariates.p-value: 0.00195% CI: [-10.55, -2.58]cLDA
Secondary
Pembro Combo vs SOC: Change From Baseline to Week 18 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the GHS question How would you rate your overall health during the past week? (Item 29) and the QoL question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro combo arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro mono arm and SOC arm and is presented earlier in the record.
Time frame: Baseline, Week 18
Population: Participants in the pembro combo arm and SOC arm who received ≥1 dose of study drug and who had EORTC-QLQ-C30 assessments available at baseline or post-baseline up to Week 18. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: Change From Baseline to Week 18 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | -0.09 Score on a Scale |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: Change From Baseline to Week 18 in the EORTC QLQ-C30 Global Health Status/Quality of Life (Items 29 and 30) Combined Score | -2.07 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between all participants of the pembro combo arm and the SOC arm. Comparison based on cLDA model with GHS/QoL score as response variable and treatment by visit interaction and stratification factors (geographic region, disease status, and fluoropyrimidine treatment) as covariates.p-value: 0.36895% CI: [-2.34, 6.31]cLDA
Secondary
Pembro Combo vs SOC: Duration of Response (DOR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 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. DOR is reported here for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro mono arm and SOC arm and is presented later in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro combo arm and SOC arm and who demonstrated a confirmed CR or PR were analyzed. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: Duration of Response (DOR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | NA Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: Duration of Response (DOR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | NA Months |
Secondary
Pembro Combo vs SOC: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro combo arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro combo arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro mono arm and SOC arm and is presented later in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro combo arm and SOC arm were analyzed. Per protocol, the pembro mono arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + SOC Chemotherapy (Pembro Combo) | Pembro Combo vs SOC: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 48.6 Percentage of Participants |
| Placebo + SOC Chemotherapy (SOC) | Pembro Combo vs SOC: Objective Response Rate (ORR) Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 37.2 Percentage of Participants |
Comparison: ORR in CPS ≥1 participants of the pembro combo arm was compared to ORR in CPS ≥1 participants of the SOC arm based on Miettinen \& Nurminen method stratified by geographic region, disease status, and Fluoropyrimidine treatment.p-value: 0.0044795% CI: [2.9, 20]Miettinen & Nurminen method
Secondary
Pembro Mono vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-Module for Gastric Cancer (STO22) Pain Symptom Subscale Score
EORTC-QLQ-STO22 is a 22-item questionnaire developed to assess QoL of gastric cancer participants. It consists of 5 multi-item subscales that assess dysphagia (3 items), dietary restriction (4 items), pain (4 items), upper gastro-esophageal symptoms (3 items), and emotional problems (3 items), and questions on dry mouth, taste, body image, and hair loss. Participant responses to the Pain symptom subscale (Items 34-37) were scored on a 4-point scale (1=Not at all to 4=Very much). Raw scores were standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating more problems. Per protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared between the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the EORTC-QLQ-STO22 Pain score was compared separately between the pembro combo arm and SOC arm and is presented later in the record.
Time frame: Baseline, Week 18
Population: Participants in the pembro mono arm and SOC arm who received ≥1 dose of study drug and who had EORTC-QLQ-STO22 assessments available at baseline or post-baseline up to Week 18. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-Module for Gastric Cancer (STO22) Pain Symptom Subscale Score | -1.14 Score on a Scale |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs. SOC: Change From Baseline to Week 18 in EORTC QLQ-Module for Gastric Cancer (STO22) Pain Symptom Subscale Score | -3.49 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-STO22 Pain symptom subscale score was compared between all participants of the pembro mono arm and the SOC arm. Comparison based on cLDA model with GHS/QoL score as response variable and treatment by visit interaction and stratification factors (geographic region, disease status, and fluoropyrimidine treatment) as covariates.p-value: 0.30895% CI: [-2.18, 6.89]cLDA
Secondary
Pembro Mono vs SOC: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score
The EORTC-QLQ-C30 is a 30-item questionnaire developed to assess the quality of life of cancer patients. Participant responses to the Global Health Status (GHS) question How would you rate your overall health during the past week? (Item 29) and the Quality of Life (QoL) question How would you rate your overall quality of life during the past week? (Item 30) were scored on a 7-point scale (1=Very Poor to 7=Excellent). Using linear transformation, raw scores were standardized so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. Per protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared between all participants of the pembro mono arm and the SOC arm as a pre-specified secondary analysis. As specified by the protocol, change from baseline to Week 18 in the GHS/QoL combined score was compared separately between all participants of the pembro combo arm and SOC arm and is presented later in the record.
Time frame: Baseline, Week 18
Population: Participants in the pembro mono arm and SOC arm who received ≥1 dose of study drug and who had EORTC-QLQ-C30 assessments available at baseline or post-baseline up to Week 18. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | -1.91 Score on a Scale |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: Change From Baseline to Week 18 in the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score | -1.75 Score on a Scale |
Comparison: Change from baseline to Week 18 in EORTC-QLQ-C30 GHS/QoL combined score was compared between all participants of the pembro mono arm and the SOC arm. Comparison based on constrained longitudinal data analysis (cLDA) model with GHS/QoL score as response variable and treatment by visit interaction and stratification factors (geographic region, disease status, and fluoropyrimidine treatment) as covariates.p-value: 0.94895% CI: [-5.01, 4.69]cLDA
Secondary
Pembro Mono vs SOC: DOR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
For participants who demonstrated a confirmed CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1 based upon BICR, DOR was defined as the time from first documented evidence of confirmed CR or PR until PD or death, whichever occurred first. DOR for participants who had not progressed or died at the time of analysis was censored at the date of their last tumor assessment. Per RECIST 1.1, PD was defined as at least a 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. DOR is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants) and had CR or PR. Per protocol, DOR was compared separately between CPS ≥1 responders of the pembro combo arm and SOC arm and is presented earlier in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro mono arm and SOC arm and who demonstrated a confirmed CR or PR were analyzed. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: DOR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | NA Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: DOR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | NA Months |
Secondary
Pembro Mono vs SOC: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
ORR was defined as the percentage of participants in the analysis population who have a CR (disappearance of all target lesions) or PR (≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. based upon BICR. Per protocol, ORR in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. The percentage of participants who experienced CR or PR is reported here as the ORR for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, ORR was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro mono arm and SOC arm were analyzed. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 14.8 Percentage of Participants |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: ORR Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 37.2 Percentage of Participants |
Comparison: ORR in CPS ≥1 participants of the pembro mono arm was compared to ORR in CPS ≥1 participants of the SOC arm based on Miettinen \& Nurminen method stratified by geographic region, disease status, and Fluoropyrimidine treatment.p-value: >0.9999995% CI: [-29.6, -14.9]Miettinen & Nurminen method
Secondary
Pembro Mono vs SOC: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants)
PFS was defined as the time from randomization to the first documented PD per RECIST 1.1 based on BICR, or death due to any cause, whichever occurred 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. Per protocol, PFS in the pembro mono arm was compared to the SOC arm as a pre-specified secondary analysis of the ITT population. PFS is reported here for all participants in the pembro mono arm and SOC arm who were PD-L1 CPS ≥1 (all participants). Per protocol, PFS was compared separately between CPS ≥1 participants of the pembro combo arm and SOC arm and is presented earlier in the record.
Time frame: Up to approximately 42 months
Population: All CPS ≥1 participants in the ITT population randomized to the pembro mono arm and SOC arm were analyzed. Per protocol, the pembro combo arm was compared to the SOC arm separately and not included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab Monotherapy (Pembro Mono) | Pembro Mono vs SOC: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 2.0 Months |
| Placebo + SOC Chemotherapy (SOC) | Pembro Mono vs SOC: PFS Per RECIST 1.1 by BICR in Participants With PD-L1 CPS ≥1 (All Participants) | 6.4 Months |
Comparison: PFS in CPS ≥1 participants of the pembro mono arm was compared to PFS in CPS ≥1 participants of the SOC arm based on a Cox regression model with Efron's method of tie handling with treatment as a covariate with stratification according to geographic region, disease status, and fluoropyrimidine treatment.p-value: 195% CI: [1.36, 1.98]Regression, Cox