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Pembrolizumab (MK-3475) Plus Chemotherapy Versus Placebo Plus Chemotherapy in Participants Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma (MK-3475-859/KEYNOTE-859)-China Extension

Phase 3
Withdrawn
Conditions
Stomach Neoplasms
Interventions
Registration Number
NCT04859582
Lead Sponsor
Merck Sharp & Dohme LLC
Brief Summary

The purpose of this study is to evaluate the efficacy of pembrolizumab (MK-3745) in combination with chemotherapy (Cisplatin combined with 5-Fluorouracil \[FP regimen\] or oxaliplatin combined with capecitabine \[CAPOX regimen\]) versus placebo in combination with chemotherapy (FP or CAPOX regimens) in the treatment of human epidermal growth factor receptor 2 (HER2) negative advanced gastric or GEJ adenocarcinoma in adult Chinese participants.

The primary hypotheses of this study are that pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy in terms of overall survival (OS).

Detailed Description

The China extension study will include participants previously enrolled in China in the global study for MK-3475-859 (NCT03675737) plus those enrolled during the China extension enrollment period. A total of approximately 231 Chinese participants will be enrolled.

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo + FP or CAPOXPlacebo for PembrolizumabParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Pembrolizumab + FP or CAPOXPembrolizumabParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Pembrolizumab + FP or CAPOXCisplatinParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Pembrolizumab + FP or CAPOXOxaliplatinParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Pembrolizumab + FP or CAPOX5-fluorouracilParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Pembrolizumab + FP or CAPOXCapecitabineParticipants receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5-fluorouracil (5FU) 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally twice a day (BID) on Days 1 to 14 Q3W. Participants who complete 35 administrations or achieve a complete response (CR) but progress after discontinuation can initiate a second course of pembrolizumab for up to 17 cycles (approximately 1 additional year).
Placebo + FP or CAPOXCisplatinParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Placebo + FP or CAPOX5-fluorouracilParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Placebo + FP or CAPOXOxaliplatinParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Placebo + FP or CAPOXCapecitabineParticipants receive placebo for pembrolizumab IV on Day 1 Q3W for up to 35 cycles (approximately 2 years) + physicians' choice of either cisplatin 80 mg/m\^2 IV on Day 1 Q3W and 5FU 800 mg/m\^2/day via continuous IV infusion on Days 1 to 5 Q3W OR oxaliplatin 130 mg/m\^2 IV on Day 1 Q3W + capecitabine 1000 mg/m\^2 orally BID on Days 1 to 14 Q3W.
Primary Outcome Measures
NameTimeMethod
Overall Survival (OS)Up to approximately 65 months

OS is the time from randomization to death due to any cause.

Secondary Outcome Measures
NameTimeMethod
Progression-free Survival (PFS)Up to approximately 65 months

PFS is defined as the time from randomization to the first documented disease progression or death due to any cause, whichever occurs first. Responses are according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR).

Objective Response Rate (ORR)Up to approximately 65 months

ORR was defined as the percentage of participants who have a confirmed 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, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by BICR.

Percentage of Participants Discontinuing Study Drug Due to AEsUp to approximately 36 months

Percentage of participants discontinuing study treatment due to an AE.

Percentage of Participants Experiencing Adverse Events (AEs)Up to approximately 65 months

Percentage of participants experiencing an AE defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study therapy and irrespective of causality to study treatment.

Duration of Response (DOR)Up to approximately 65 months

DOR is determined by disease assessment and is defined as the time from first response (CR or PR) to disease progression, or death from any cause, whichever occurs first.

Trial Locations

Locations (28)

Peking Union Medical College Hospital ( Site 2425)

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Beijing, Beijing, China

Fujian Medical University Union Hospital ( Site 2410)

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Fuzhou, Fujian, China

900 Hospital of the Joint ( Site 2418)

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Fuzhou, Fujian, China

Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)

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Beijing, Beijing, China

Yancheng First People s Hospital ( Site 2426)

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Yancheng, Jiangsu, China

The First Affiliated Hospital of Nanchang University ( Site 2440)

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Nanchang, Jiangxi, China

Zhejiang Provincial People's Hospital ( Site 2446)

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Hangzhou, Zhejiang, China

1st Affil hosp of Med College of Xi'an Jiaotong University ( Site 2428)

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XiAn, Shanxi, China

Fujian Provincial Cancer Hospital ( Site 2414)

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Fuzhou, Fujian, China

The First Affiliated Hospital of Xiamen University ( Site 2430)

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Xiamen, Fujian, China

Hunan Cancer Hospital ( Site 2439)

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Changsha, Hunan, China

The First Hospital of Jilin University ( Site 2416)

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Chang chun, Jilin, China

The Affiliated Hospital of Qingdao University ( Site 2405)

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Qingdao, Shandong, China

Zhongshan Hospital affiliated to Fudan University ( Site 2407)

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Shanghai, Shanghai, China

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)

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Urumqi, Xinjiang, China

Sir Run Run Show Hospital ( Site 2427)

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Hangzhou, Zhejiang, China

Zhejiang Cancer Hospital ( Site 2417)

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Hangzhou, Zhejiang, China

Zhongshan Hospital Xiamen University ( Site 2447)

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Xiamen, Fujian, China

Guangdong General Hospital ( Site 2431)

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Guangzhou, Guangdong, China

Hubei Cancer Hospital ( Site 2434)

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Wuhan, Hubei, China

Peking University Shenzhen Hospital ( Site 2442)

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Shenzhen, Guangdong, China

Henan Cancer Hospital ( Site 2415)

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Zhengzhou, Henan, China

Harbin Medical University Cancer Hospital ( Site 2401)

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Harbin, Heilongjiang, China

Xiangya Hospital Central-South University ( Site 2419)

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Changsha, Hunan, China

Changzhou Cancer Hospital-Changzhou Fourth Peoples Hospital ( Site 2441)

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Changzhou, Jiangsu, China

The 81st Hospital of PLA ( Site 2413)

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Nanjing, Jiangsu, China

Jiangsu Cancer Hospital ( Site 2432)

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Nanjing, Jiangsu, China

Shanghai East Hospital ( Site 2403)

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Shanghai, Shanghai, China

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