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

NCT ID: NCT04859582

Last Updated: 2021-12-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2018-11-08

Study Completion Date

2024-11-29

Brief Summary

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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

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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.

Conditions

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Stomach Neoplasms

Keywords

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programmed cell death 1 (PD-1, PD1) programmed cell death ligand 1 (PD-L1, PDL1) programmed cell death ligand 2 (PD-L2, PDL2)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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Pembrolizumab + FP or CAPOX

Participants 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).

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

Administered as an IV infusion on Day 1 Q3W

Cisplatin

Intervention Type DRUG

Administered as an IV infusion on Day 1 Q3W

5-fluorouracil

Intervention Type DRUG

Administered as a continuous IV infusion on Days 1-5 Q3W

Oxaliplatin

Intervention Type DRUG

Administered as an IV infusion on Day 1 Q3W

Capecitabine

Intervention Type DRUG

Administered orally BID on Days 1 to 14 Q3W

Placebo + FP or CAPOX

Participants 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.

Group Type ACTIVE_COMPARATOR

Cisplatin

Intervention Type DRUG

Administered as an IV infusion on Day 1 Q3W

5-fluorouracil

Intervention Type DRUG

Administered as a continuous IV infusion on Days 1-5 Q3W

Oxaliplatin

Intervention Type DRUG

Administered as an IV infusion on Day 1 Q3W

Capecitabine

Intervention Type DRUG

Administered orally BID on Days 1 to 14 Q3W

Placebo for Pembrolizumab

Intervention Type DRUG

Administered as an IV infusion on Day 1 Q3W

Interventions

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Pembrolizumab

Administered as an IV infusion on Day 1 Q3W

Intervention Type BIOLOGICAL

Cisplatin

Administered as an IV infusion on Day 1 Q3W

Intervention Type DRUG

5-fluorouracil

Administered as a continuous IV infusion on Days 1-5 Q3W

Intervention Type DRUG

Oxaliplatin

Administered as an IV infusion on Day 1 Q3W

Intervention Type DRUG

Capecitabine

Administered orally BID on Days 1 to 14 Q3W

Intervention Type DRUG

Placebo for Pembrolizumab

Administered as an IV infusion on Day 1 Q3W

Intervention Type DRUG

Other Intervention Names

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KEYTRUDA® MK-3475 PLATINOL® ADRUCIL® 5FU ELOXATIN® XELODA®

Eligibility Criteria

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Inclusion Criteria

* Has histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma with known programmed cell death ligand 1 (PD-L1) expression status
* Has human epidermal growth factor receptor 2 (HER2) negative cancer
* Male participants must agree to use contraception during the intervention period and for at least 95 days after the last dose of chemotherapy, refrain from donating sperm and be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent or must agree to use contraception per study protocol unless confirmed to be azoospermic during this period
* Female participants who are not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) OR is a WOCBP who agrees to use contraception or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for at least 180 days after the last dose of chemotherapy or for at least 120 days after the last dose of pembrolizumab, whichever is last, and agrees not to donate eggs to others or freeze/store for her own use for the purpose of reproduction during this period
* Has measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as assessed by investigator assessment
* Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
* Has provided tumor tissue sample deemed adequate for PD-L1 biomarker analysis
* Has provided tumor tissue sample for microsatellite instability (MSI) biomarker analysis
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 3 days prior to the start of study intervention
* Has adequate organ function as demonstrated by laboratory testing within 10 days prior to the start of study treatment

Exclusion Criteria

* Has squamous cell or undifferentiated gastric cancer
* Has had major surgery, open biopsy, or significant traumatic injury within 28 days prior to randomization, anticipation of the need for major surgery during the course of study intervention, or has not recovered adequately from the toxicity and/or complications from previous surgery
* Has preexisting peripheral neuropathy \>Grade 1
* Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation
* Has had previous therapy for locally advanced, unresectable or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant and/or adjuvant therapy as long as it was completed ≥6 months prior to randomization
* Has received prior therapy with an anti-PD-1, anti-PD-L1 or anti- PD-L2 agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), OX- 40, CD137)
* Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization or has not recovered from all AEs due to any previous therapies to ≤Grade 1 or baseline
* Has received prior radiotherapy within 2 weeks prior to study start or has not recovered from all previous radiation-related toxicities, required corticosteroids, and have not had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to noncentral nervous system (CNS) disease
* Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
* Is currently participating in 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 treatment
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment
* Has a known additional malignancy that is progressing or has required active treatment within the past 5 years with the exception of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy
* Has known active CNS metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
* Has an active autoimmune disease that has required systemic treatment in past 2 years
* Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known history of Hepatitis B (defined as Hepatitis B surface antigen \[HBsAg\] reactive) or known active Hepatitis C virus (defined as Hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] detected qualitatively) infection
* Has a known history of active tuberculosis
* Has hypokalemia (serum potassium less than the lower limit of normal)
* Has hypomagnesemia (serum magnesium less than the lower limit of normal)
* Has hypocalcemia (serum calcium less than the lower limit of normal)
* Has a history or current evidence of any condition (eg, known deficiency of the enzyme dihydropyrimidine dehydrogenase), therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
* Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 180 days after the last dose of chemotherapy or through 120 days after the last dose of pembrolizumab, whichever is last
* Has had an allogenic tissue/solid organ transplant
* Has a known severe hypersensitivity (≥ Grade 3) to any of the study chemotherapy agents (including, but not limited to, infusional 5-fluorouracil or oral capecitabine) and/or to any of their excipients
* For participants taking cisplatin: has Grade ≥2 audiometric hearing loss
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)

Beijing, Beijing Municipality, China

Site Status

Peking Union Medical College Hospital ( Site 2425)

Beijing, Beijing Municipality, China

Site Status

Fujian Medical University Union Hospital ( Site 2410)

Fuzhou, Fujian, China

Site Status

Fujian Provincial Cancer Hospital ( Site 2414)

Fuzhou, Fujian, China

Site Status

900 Hospital of the Joint ( Site 2418)

Fuzhou, Fujian, China

Site Status

The First Affiliated Hospital of Xiamen University ( Site 2430)

Xiamen, Fujian, China

Site Status

Zhongshan Hospital Xiamen University ( Site 2447)

Xiamen, Fujian, China

Site Status

Guangdong General Hospital ( Site 2431)

Guangzhou, Guangdong, China

Site Status

Peking University Shenzhen Hospital ( Site 2442)

Shenzhen, Guangdong, China

Site Status

Harbin Medical University Cancer Hospital ( Site 2401)

Harbin, Heilongjiang, China

Site Status

Henan Cancer Hospital ( Site 2415)

Zhengzhou, Henan, China

Site Status

Hubei Cancer Hospital ( Site 2434)

Wuhan, Hubei, China

Site Status

Xiangya Hospital Central-South University ( Site 2419)

Changsha, Hunan, China

Site Status

Hunan Cancer Hospital ( Site 2439)

Changsha, Hunan, China

Site Status

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

Changzhou, Jiangsu, China

Site Status

The 81st Hospital of PLA ( Site 2413)

Nanjing, Jiangsu, China

Site Status

Jiangsu Cancer Hospital ( Site 2432)

Nanjing, Jiangsu, China

Site Status

Yancheng First People s Hospital ( Site 2426)

Yancheng, Jiangsu, China

Site Status

The First Affiliated Hospital of Nanchang University ( Site 2440)

Nanchang, Jiangxi, China

Site Status

The First Hospital of Jilin University ( Site 2416)

Changchun, Jilin, China

Site Status

The Affiliated Hospital of Qingdao University ( Site 2405)

Qingdao, Shandong, China

Site Status

Shanghai East Hospital ( Site 2403)

Shanghai, Shanghai Municipality, China

Site Status

Zhongshan Hospital affiliated to Fudan University ( Site 2407)

Shanghai, Shanghai Municipality, China

Site Status

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

XiAn, Shanxi, China

Site Status

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)

Ürümqi, Xinjiang, China

Site Status

Zhejiang Provincial People's Hospital ( Site 2446)

Hangzhou, Zhejiang, China

Site Status

Sir Run Run Show Hospital ( Site 2427)

Hangzhou, Zhejiang, China

Site Status

Zhejiang Cancer Hospital ( Site 2417)

Hangzhou, Zhejiang, China

Site Status

Countries

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China

Related Links

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http://merckoncologyclinicaltrials.com

Merck Oncology Clinical Trials Information

Other Identifiers

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2018-001757-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MK-3475-859 China Extension

Identifier Type: OTHER

Identifier Source: secondary_id

KEYNOTE-859

Identifier Type: OTHER

Identifier Source: secondary_id

194649

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-859 China Extension

Identifier Type: -

Identifier Source: org_study_id