Study of Pembrolizumab (MK-3475) as First-Line Monotherapy and Combination Therapy for Treatment of Advanced Gastric or Gastroesophageal Junction Adenocarcinoma (MK-3475-062/KEYNOTE-062)

NCT02494583 | Completed Phase 3 Results DMC FDA Drug

• 5 other identifiers: 3475-062163187MK-3475-062KEYNOTE-0622015-000972-88
• Study Type: interventional
• Target: 763
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Gastric Adenocarcinoma

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)

Outcome Measures

Primary Outcomes (5)

• 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.

  Up to approximately 36 months

• 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.

  Up to approximately 42 months

• 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.

  Up to approximately 42 months

• 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.

  Up to approximately 42 months

• 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.

  Up to approximately 42 months

Secondary Outcomes (11)

• 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

• 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

• 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

• 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

• 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

Study Arms (3)

Pembrolizumab Monotherapy (Pembro Mono)

EXPERIMENTAL

Participants will receive pembrolizumab 200 mg intravenously (IV) on Day 1 of each 3-week cycle (Q3W). Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Biological: Pembrolizumab

Pembrolizumab + SOC Chemotherapy (Pembro Combo)

EXPERIMENTAL

Participants will receive pembrolizumab 200 mg 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 twice a day (BID) on Days 1-14 Q3W may be substituted for 5-FU per local guidelines. Eligible participants who stop pembrolizumab with Stable Disease (SD) or better but progress after discontinuation may be able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Biological: Pembrolizumab; Drug: Cisplatin; Drug: 5-FU; Drug: Capecitabine

Placebo + SOC Chemotherapy (SOC)

PLACEBO COMPARATOR

Participants receive 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 may be substituted for 5-FU per local guidelines.

Drug: Cisplatin; Drug: 5-FU; Drug: Capecitabine; Drug: Placebo

Interventions

Pembrolizumab BIOLOGICAL

Pembrolizumab 200 mg IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab + SOC Chemotherapy (Pembro Combo); Pembrolizumab Monotherapy (Pembro Mono)

Cisplatin DRUG

Cisplatin 80 mg/m\^2 IV on Day 1 of each week in 3-week cycles (6 cycle maximum per local country guidelines).

Pembrolizumab + SOC Chemotherapy (Pembro Combo); Placebo + SOC Chemotherapy (SOC)

5-FU DRUG

5-FU 800 mg/m\^2/day IV continuous from Day 1-5 of each 3-week cycle.

Pembrolizumab + SOC Chemotherapy (Pembro Combo); Placebo + SOC Chemotherapy (SOC)

Capecitabine DRUG

Capecitabine 1000 mg/m\^2 twice daily by oral tablet on Day 1-14 of each 3-week cycle.

Pembrolizumab + SOC Chemotherapy (Pembro Combo); Placebo + SOC Chemotherapy (SOC)

Placebo DRUG

Normal saline IV on Day 1 of each week in 3-week cycles for up to 35 cycles (approximately 2 years).

Placebo + SOC Chemotherapy (SOC)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (6)

• Janjigian YY, Cecchini M, Shitara K, Enzinger PC, Wainberg ZA, Chau I, Satoh T, Lee J, Nebozhyn M, Loboda A, Kobie J, Vajdi A, Shih CS, Cristescu R, Cao ZA. Genomic Landscape of Late-Stage Gastric Cancer: Analysis From KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Studies. JCO Precis Oncol. 2025 Mar;9:e2400456. doi: 10.1200/PO-24-00456. Epub 2025 Mar 21.

  PMID: 40117530 DERIVED

• Muro K, Shitara K, Yamaguchi K, Yoshikawa T, Satake H, Hara H, Sugimoto N, Machida N, Goto M, Kawakami H, Amagai K, Omuro Y, Esaki T, Hironaka S, Nishina T, Komatsu Y, Matsubara H, Shiratori S, Han S, Satoh T, Ohtsu A. Efficacy of Pembrolizumab Monotherapy in Japanese Patients with Advanced Gastric or Gastroesophageal Junction Cancer. J Gastrointest Cancer. 2023 Sep;54(3):951-961. doi: 10.1007/s12029-023-00920-9. Epub 2023 Apr 10.

  PMID: 37037952 DERIVED

• Satake H, Lee KW, Chung HC, Lee J, Yamaguchi K, Chen JS, Yoshikawa T, Amagai K, Yeh KH, Goto M, Chao Y, Lam KO, Han SR, Shiratori S, Shah S, Shitara K. Pembrolizumab or pembrolizumab plus chemotherapy versus standard of care chemotherapy in patients with advanced gastric or gastroesophageal junction adenocarcinoma: Asian subgroup analysis of KEYNOTE-062. Jpn J Clin Oncol. 2023 Mar 7;53(3):221-229. doi: 10.1093/jjco/hyac188.

  PMID: 36533429 DERIVED

• Lee KW, Van Cutsem E, Bang YJ, Fuchs CS, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Chao J, Wainberg ZA, Cao ZA, Aurora-Garg D, Kobie J, Cristescu R, Bhagia P, Shah S, Tabernero J, Shitara K, Wyrwicz L. Association of Tumor Mutational Burden with Efficacy of Pembrolizumab+/-Chemotherapy as First-Line Therapy for Gastric Cancer in the Phase III KEYNOTE-062 Study. Clin Cancer Res. 2022 Aug 15;28(16):3489-3498. doi: 10.1158/1078-0432.CCR-22-0121.

  PMID: 35657979 DERIVED

• Chao J, Fuchs CS, Shitara K, Tabernero J, Muro K, Van Cutsem E, Bang YJ, De Vita F, Landers G, Yen CJ, Chau I, Elme A, Lee J, Ozguroglu M, Catenacci D, Yoon HH, Chen E, Adelberg D, Shih CS, Shah S, Bhagia P, Wainberg ZA. Assessment of Pembrolizumab Therapy for the Treatment of Microsatellite Instability-High Gastric or Gastroesophageal Junction Cancer Among Patients in the KEYNOTE-059, KEYNOTE-061, and KEYNOTE-062 Clinical Trials. JAMA Oncol. 2021 Jun 1;7(6):895-902. doi: 10.1001/jamaoncol.2021.0275.

  PMID: 33792646 DERIVED

• Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. doi: 10.1001/jamaoncol.2020.3370.

  PMID: 32880601 DERIVED

Related Links

• Merck Oncology Clinical Trial Information

MeSH Terms

Conditions

Stomach Neoplasms; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Cisplatin; Fluorouracil; 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; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 10, 2015
• Study Start: July 31, 2015
• Primary Completion: March 26, 2019
• Study Completion: June 6, 2022
• Last Updated: April 13, 2023
• Results First Posted: March 13, 2020

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share