Gastric Cancer, Gastroesophageal Junction Cancer
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Brief summary
The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in the neoadjuvant (prior to surgery) or adjuvant (after surgery) treatment of previously untreated adults with gastric and gastroesophageal junction (GEJ) adenocarcinoma. The primary study hypotheses are that: * Neoadjuvant and adjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab is superior to neoadjuvant and adjuvant placebo plus chemotherapy, followed by adjuvant placebo in terms of Event-free Survival (EFS) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), and * Neoadjuvant pembrolizumab plus chemotherapy is superior to neoadjuvant placebo plus chemotherapy in terms of rate of Pathological Complete Response (pathCR) at the time of surgery. With Amendment 10, upon study completion, participants will be discontinued and may be enrolled in an extension study.
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGPlacebo
IV infusion
DRUGCisplatin
IV infusion
DRUGCapecitabine
Oral tablets
DRUG5-fluorouracil
IV infusion
DRUGDocetaxel
IV infusion
DRUGOxaliplatin
IV infusion
DRUGLeucovorin
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has previously untreated localized gastric or GEJ adenocarcinoma as defined by T3 or greater primary lesion or the presence of any positive nodes - N+ (clinical nodes) without evidence of metastatic disease. * Plans to proceed to surgery following pre-operative chemotherapy based on standard staging studies per local practice. * Is willing to provide tissue from a tumor lesion at baseline and at time of surgery. * Has an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1 within 3 days prior to the first dose of study treatment. * Has adequate organ function. * Male participants of childbearing potential must agree to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy. * Female participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater. * Has life expectancy of greater than 6 months.
Exclusion criteria
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has an active infection requiring systemic therapy. * Is currently participating in or has participated in a trial of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment. * Has received prior therapy with an anti-programmed cell death protein-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (i.e., cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], tumor necrosis factor receptor superfamily member 4 \[OX-40\], necrosis factor receptor superfamily member 9 \[CD137\]) or has previously participated in a MSD pembrolizumab (MK-3475) clinical study. * Has received prior systemic anti-cancer therapy including investigational agents for the current malignancy. * Has a 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 14 days prior the first dose of study treatment. * Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ that have undergone potentially curative therapy are not excluded. * Has a known severe hypersensitivity (≥ Grade 3) to pembrolizumab, its active substance and/or any of its excipients, or to any of the study chemotherapy agents and/or to any of their excipients. * Has an active autoimmune disease that has required systemic treatment in past 2 years. * Has a known history of human immunodeficiency virus (HIV) infection. * Has a known history of Hepatitis B or known active Hepatitis C virus infection. * Has a known history of active tuberculosis (TB). * Female participants who are pregnant or breastfeeding or expecting to conceive children within the projected duration of the study, starting with the screening visit through180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is greater. * Male participants who are expecting to father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy. * Has had an allogenic tissue/solid organ transplant. * Has received a live vaccine within 30 days prior to the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | Up to approximately 75 months | EFS was based on RECIST 1.1 as assessed by the investigator and was defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who were disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who were confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), were not considered EFS events. |
| Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18) | PathCR rate was defined as the percentage of participants having a pathCR based on central review. pathCR was defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes. The percentage of participants having pathCR was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms. |
| Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | Up to approximately 75 months | OS was defined as the time from randomization to death due to any cause. OS was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms. |
| Number of Participants Who Experienced One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 70 months | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE was presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts. |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 17 months | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE was presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 89 months | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced at least one AE was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts. |
| Number of Participants Who Discontinued Study Treatment Due to an AE - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 17 months | An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts. |
| Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | Up to approximately 75 months | DFS was defined as the time from post-surgery baseline scan until the first occurrence of local or distant recurrence or death from any cause and was based on RECIST 1.1 as assessed by the investigator. |
| Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 75 months | OS was defined as the time from randomization to death due to any cause. OS was presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts. |
| Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | Up to approximately 75 months | EFS was based on RECIST 1.1 as assessed by the investigator and was defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who were disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who were confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), were not considered EFS events. |
Countries
Belgium, Brazil, Canada, Chile, China, Estonia, France, Germany, Guatemala, Israel, Italy, Japan, Latvia, Lithuania, Malaysia, Philippines, Poland, Russia, Singapore, South Korea, Taiwan, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Participant flow
Pre-assignment details
Of the 1007 participants that were randomized to trial, 1001 received treatment.
Participants by arm
| Arm | Count |
|---|---|
| Pembrolizumab + XP/FP XP=cisplatin+capecitabine and FP=cisplatin+5-fluorouracil. Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets twice each day (BID) on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle.
Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles. | 402 |
| Placebo + XP/FP Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle.
Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and capecitabine 1000 mg/m\^2 via oral tablets BID on Days 1 to 14 of each 3-week cycle OR cisplatin 80 mg/m\^2 via IV infusion on Day 1 Q3W and 5FU 800 mg/m\^2 via continuous IV infusion on Days 1 to 5 of each 3-week cycle, followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles. | 402 |
| Pembrolizumab + FLOT Cohort FLOT=docetaxel+oxaliplatin+5FU+leucovorin (calcium folinate). Neoadjuvant: Prior to surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin (calcium folinate) 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations).
Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of pembrolizumab 200 mg via IV infusion Day 1 Q3W PLUS docetaxel 50 mg/m\^2, oxaliplatin 85 mg/m\^2, 5FU 2600 mg/m\^2, and leucovorin 200 mg/m\^2 Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by pembrolizumab monotherapy 200 mg via IV infusion on Day 1 Q3W for up to 11 additional cycles. | 100 |
| Placebo + FLOT Cohort Neoadjuvant: Prior to surgery, participants receive 3 cycles of placebo (normal saline solution) via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations).
Adjuvant: 4 to 10 weeks post-surgery, participants receive 3 cycles of placebo via IV infusion on Day 1 Q3W PLUS docetaxel 50 mg/m\^2 via IV infusion, oxaliplatin 85 mg/m\^2 via IV infusion, 5FU 2600 mg/m\^2 via IV infusion, and leucovorin 200 mg/m\^2 via IV infusion Q2W (on Days 1 and 15 of Cycle 1; Day 8 of Cycle 2, and Day 1 of Cycle 3, for 4 administrations), followed by placebo monotherapy via IV infusion on Day 1 Q3W for up to 11 additional cycles. | 103 |
| Total | 1,007 |
Baseline characteristics
| Characteristic | Total | Placebo + FLOT Cohort | Pembrolizumab + FLOT Cohort | Placebo + XP/FP | Pembrolizumab + XP/FP |
|---|---|---|---|---|---|
| Age, Customized 85 years and older | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Customized Adults (between 18 and 64 years) | 550 Participants | 64 Participants | 58 Participants | 221 Participants | 207 Participants |
| Age, Customized From 65 to 84 years | 456 Participants | 39 Participants | 42 Participants | 181 Participants | 194 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 118 Participants | 9 Participants | 11 Participants | 54 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 839 Participants | 94 Participants | 89 Participants | 323 Participants | 333 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 50 Participants | 0 Participants | 0 Participants | 25 Participants | 25 Participants |
| Geographic Region Asia | 387 Participants | 3 Participants | 3 Participants | 191 Participants | 190 Participants |
| Geographic Region ROW | 270 Participants | 23 Participants | 32 Participants | 110 Participants | 105 Participants |
| Geographic Region US | 25 Participants | 7 Participants | 9 Participants | 6 Participants | 3 Participants |
| Geographic Region Western Europe | 325 Participants | 70 Participants | 56 Participants | 95 Participants | 104 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 395 Participants | 4 Participants | 4 Participants | 193 Participants | 194 Participants |
| Race (NIH/OMB) Black or African American | 11 Participants | 2 Participants | 1 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 14 Participants | 0 Participants | 2 Participants | 7 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 45 Participants | 0 Participants | 0 Participants | 23 Participants | 22 Participants |
| Race (NIH/OMB) White | 541 Participants | 97 Participants | 92 Participants | 174 Participants | 178 Participants |
| Sex: Female, Male Female | 283 Participants | 32 Participants | 22 Participants | 115 Participants | 114 Participants |
| Sex: Female, Male Male | 724 Participants | 71 Participants | 78 Participants | 287 Participants | 288 Participants |
| Tumor Staging Missing | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Tumor Staging Stage II | 215 Participants | 31 Participants | 22 Participants | 80 Participants | 82 Participants |
| Tumor Staging Stage III | 748 Participants | 66 Participants | 74 Participants | 306 Participants | 302 Participants |
| Tumor Staging Stage IVa | 43 Participants | 6 Participants | 4 Participants | 15 Participants | 18 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 | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 200 / 402 | 225 / 402 | 40 / 100 | 56 / 103 | 240 / 502 | 281 / 505 |
| other Total, other adverse events | 392 / 399 | 392 / 400 | 99 / 99 | 103 / 103 | 491 / 498 | 495 / 503 |
| serious Total, serious adverse events | 174 / 399 | 160 / 400 | 66 / 99 | 51 / 103 | 240 / 498 | 211 / 503 |
Outcome results
Primary
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by computer tomography (CT) scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Time frame: Up to approximately 75 months
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms, as pre-specified per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + XP/FP | Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 44.4 Months |
| Placebo + XP/FP | Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 25.7 Months |
p-value: 0.0150195% CI: [0.67, 0.98]Log Rank
Primary
Number of Participants Who Discontinue Study Treatment Due to an AE - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE is presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 17 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment in the Pembrolizumab+FLOT and Placebo+FLOT Cohort treatment arms, as pre-specified per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + XP/FP | Number of Participants Who Discontinue Study Treatment Due to an AE - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 37 Participants |
| Placebo + XP/FP | Number of Participants Who Discontinue Study Treatment Due to an AE - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 26 Participants |
Primary
Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE is presented for the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 70 months
Population: The analysis population consisted of all participants who received ≥1 dose of study treatment in the Pembrolizumab+FLOT and Placebo+FLOT Cohort treatment arms, as pre-specified per protocol.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pembrolizumab + XP/FP | Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 99 Participants |
| Placebo + XP/FP | Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 103 Participants |
Primary
Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
OS is defined as the time from randomization to death due to any cause. OS is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.
Time frame: Up to approximately 75 months
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms, as pre-specified per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + XP/FP | Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 71.8 Months |
| Placebo + XP/FP | Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 55.7 Months |
p-value: 0.0750395% CI: [0.71, 1.06]Log Rank
Primary
Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
PathCR rate is defined as the percentage of participants having a pathCR based on central review. pathCR is defined as no invasive disease within an entirely submitted and evaluated gross lesion, and histologically negative nodes. The percentage of participants having pathCR is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms.
Time frame: Up to approximately 9 weeks following completion of neoadjuvant treatment (up to Study Week 18)
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms, as pre-specified per protocol.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pembrolizumab + XP/FP | Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 13.4 Percentage of Participants |
| Placebo + XP/FP | Pathological Complete Response (pathCR) Rate - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 2.0 Percentage of Participants |
p-value: <0.0000195% CI: [8, 15.3]Stratified Miettinen and Nurminen
Secondary
Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms
DFS is defined as the time from post-surgery baseline scan until the first occurrence of local or distant recurrence or death from any cause and is based on RECIST 1.1 as assessed by the investigator.
Time frame: Up to approximately 75 months
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms who had surgery, as pre-specified per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + XP/FP | Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 66.1 Months |
| Placebo + XP/FP | Disease-free Survival (DFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms | 44.2 Months |
p-value: 0.0412595% CI: [0.65, 1.03]Log Rank
Secondary
Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
EFS is based on RECIST 1.1 as assessed by the investigator and is defined as the time from randomization to the first of the following events: radiographic disease progression per RECIST 1.1; local or distant recurrence as assessed by CT scan or biopsy if indicated (for participants who are disease free after surgery); clinical progression as evidenced by peritoneal carcinomatosis confirmed by preoperative laparoscopy or laparotomy (for participants who are confirmed to be free of peritoneal involvement by laparoscopy at screening); or death due to any cause. A second primary malignancy, or radiographic progressive disease (PD) during the neoadjuvant phase that does not preclude successful surgery (i.e., disease free after surgery), are not considered EFS events.
Time frame: Up to approximately 75 months
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts, as pre-specified per protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + XP/FP | Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 47.0 Months |
| Placebo + XP/FP | Event-free Survival (EFS) Per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 26.9 Months |
p-value: 0.0058995% CI: [0.67, 0.95]Log Rank
Secondary
Number of Participants Who Discontinue Study Treatment Due to an AE - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be presented the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 18 months
Secondary
Number of Participants Who Experience One or More Adverse Events (AEs) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms Separately and in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms separately and in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 75 months
Secondary
Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts
OS is defined as the time from randomization to death due to any cause. OS is presented for the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts.
Time frame: Up to approximately 75 months
Population: The analysis population consisted of all randomized participants in the Pembrolizumab+XP/FP and Placebo+XP/FP treatment arms in combination with the Pembrolizumab+FLOT and Placebo+FLOT Cohorts, as pre-specified in the protocol.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pembrolizumab + XP/FP | Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | NA Months |
| Placebo + XP/FP | Overall Survival (OS) - Pembrolizumab+XP/FP and Placebo+XP/FP Treatment Arms in Combination With the Pembrolizumab+FLOT and Placebo+FLOT Cohorts | 55.7 Months |
p-value: 0.0449395% CI: [0.71, 1.03]Log Rank