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

NCT04859582 | Withdrawn Phase 3 DMC FDA Drug

• 5 other identifiers: 3475-859 China Extension2018-001757-27MK-3475-859 China ExtensionKEYNOTE-859194649
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 28

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).

Conditions

Stomach Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

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

  Up to approximately 65 months

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Up to approximately 65 months

• Objective Response Rate (ORR)

  Up to approximately 65 months

• Duration of Response (DOR)

  Up to approximately 65 months

• Percentage of Participants Experiencing Adverse Events (AEs)

  Up to approximately 65 months

• Percentage of Participants Discontinuing Study Drug Due to AEs

  Up to approximately 36 months

Study Arms (2)

Pembrolizumab + FP or CAPOX

EXPERIMENTAL

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).

Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Capecitabine

Placebo + FP or CAPOX

ACTIVE COMPARATOR

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.

Drug: Cisplatin; Drug: 5-fluorouracil; Drug: Oxaliplatin; Drug: Capecitabine; Drug: Placebo for Pembrolizumab

Interventions

Pembrolizumab BIOLOGICAL

Administered as an IV infusion on Day 1 Q3W

Also known as: KEYTRUDA®, MK-3475

Pembrolizumab + FP or CAPOX

Cisplatin DRUG

Administered as an IV infusion on Day 1 Q3W

Also known as: PLATINOL®

Pembrolizumab + FP or CAPOX; Placebo + FP or CAPOX

5-fluorouracil DRUG

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

Also known as: ADRUCIL®, 5FU

Pembrolizumab + FP or CAPOX; Placebo + FP or CAPOX

Oxaliplatin DRUG

Administered as an IV infusion on Day 1 Q3W

Also known as: ELOXATIN®

Pembrolizumab + FP or CAPOX; Placebo + FP or CAPOX

Capecitabine DRUG

Administered orally BID on Days 1 to 14 Q3W

Also known as: XELODA®

Pembrolizumab + FP or CAPOX; Placebo + FP or CAPOX

Placebo for Pembrolizumab DRUG

Administered as an IV infusion on Day 1 Q3W

Placebo + FP or CAPOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (28)

Cancer Hospital Chinese Academy of Medical Sciences ( Site 2421)

Beijing, Beijing Municipality, 100021, China

Location

Peking Union Medical College Hospital ( Site 2425)

Beijing, Beijing Municipality, 100730, China

Location

Fujian Medical University Union Hospital ( Site 2410)

Fuzhou, Fujian, 350001, China

Location

Fujian Provincial Cancer Hospital ( Site 2414)

Fuzhou, Fujian, 350014, China

Location

900 Hospital of the Joint ( Site 2418)

Fuzhou, Fujian, 350025, China

Location

The First Affiliated Hospital of Xiamen University ( Site 2430)

Xiamen, Fujian, 361003, China

Location

Zhongshan Hospital Xiamen University ( Site 2447)

Xiamen, Fujian, 361004, China

Location

Guangdong General Hospital ( Site 2431)

Guangzhou, Guangdong, 510080, China

Location

Peking University Shenzhen Hospital ( Site 2442)

Shenzhen, Guangdong, 518036, China

Location

Harbin Medical University Cancer Hospital ( Site 2401)

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital ( Site 2415)

Zhengzhou, Henan, 450008, China

Location

Hubei Cancer Hospital ( Site 2434)

Wuhan, Hubei, 430079, China

Location

Xiangya Hospital Central-South University ( Site 2419)

Changsha, Hunan, 410008, China

Location

Hunan Cancer Hospital ( Site 2439)

Changsha, Hunan, 410013, China

Location

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

Changzhou, Jiangsu, 213032, China

Location

The 81st Hospital of PLA ( Site 2413)

Nanjing, Jiangsu, 210002, China

Location

Jiangsu Cancer Hospital ( Site 2432)

Nanjing, Jiangsu, 210009, China

Location

Yancheng First People s Hospital ( Site 2426)

Yancheng, Jiangsu, 224000, China

Location

The First Affiliated Hospital of Nanchang University ( Site 2440)

Nanchang, Jiangxi, 330006, China

Location

The First Hospital of Jilin University ( Site 2416)

Changchun, Jilin, 130021, China

Location

The Affiliated Hospital of Qingdao University ( Site 2405)

Qingdao, Shandong, 266061, China

Location

Shanghai East Hospital ( Site 2403)

Shanghai, Shanghai Municipality, 200120, China

Location

Zhongshan Hospital affiliated to Fudan University ( Site 2407)

Shanghai, Shanghai Municipality, 210000, China

Location

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

XiAn, Shanxi, 710061, China

Location

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 2420)

Ürümqi, Xinjiang, 830001, China

Location

Zhejiang Provincial People's Hospital ( Site 2446)

Hangzhou, Zhejiang, 310014, China

Location

Sir Run Run Show Hospital ( Site 2427)

Hangzhou, Zhejiang, 310016, China

Location

Zhejiang Cancer Hospital ( Site 2417)

Hangzhou, Zhejiang, 310022, China

Location

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Cisplatin; Fluorouracil; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: April 26, 2021
• Study Start: November 8, 2018
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: December 16, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (28)