A Study of Pembrolizumab (MK-3475) Versus Paclitaxel for Participants With Advanced Gastric/Gastroesophageal Junction Adenocarcinoma That Progressed After Therapy With Platinum and Fluoropyrimidine (MK-3475-061/KEYNOTE-061)

NCT02370498 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 3475-061152988MK-3475-0612014-005241-45
• Study Type: interventional
• Target: 592
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a study for participants with advanced gastric or gastroesophageal junction adenocarcinoma who have had tumor progression after first-line treatment with platinum and fluoropyrimidine doublet therapy. The primary study hypotheses are that pembrolizumab (MK-3475) prolongs progression free survival (PFS) and overall survival (OS) for participants with tumors that show positive programmed cell death ligand 1 (PD-L1) expression. As of 20-March-2016, enrollment will be limited to PD-L1 positive participants.

Conditions

Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Gastric cancer; Gastroesophageal junction cancer; PD1; PD-1; PDL1; PD-L1

Outcome Measures

Primary Outcomes (2)

• Progression-free Survival (PFS) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Based on Blinded Independent Central Review (BICR) in Programmed Death-Ligand 1 (PD-L1) Positive Participants

  PFS was defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on BICR, or death due to any cause, whichever occurs first. According to RECIST 1.1, progressive disease (PD) was defined as a 20% relative increase in the sum of diameters (SOD) of target lesions, taking as reference the nadir SOD and an absolute increase of \>5 mm in the SOD, or the appearance of new lesions. PFS was analyzed using the Kaplan-Meier method and median PFS (95% confidence interval \[CI\]) in months was reported for PD-L1 positive participants by treatment group.

  Up to 30 months (through database cut-off date of 26 Oct 2017)

• Overall Survival (OS) in PD-L1 Positive 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. OS was analyzed using the Kaplan-Meier method and median OS (95% CI) in months was reported for PD-L1 positive participants by treatment group.

  Up to 30 months (through database cut-off date of 26 Oct 2017)

Secondary Outcomes (22)

• PFS According to RECIST 1.1 Based on BICR in All Participants

  Up to 30 months (through database cut-off date of 26 Oct 2017)

• OS in All Participants

  Up to 30 months (through database cut-off date of 26 Oct 2017)

• PFS According to RECIST 1.1 Based on Investigator Assessment in PD-L1 Positive Participants

  Up to 30 months (through database cut-off date of 26 Oct 2017)

• PFS According to RECIST 1.1 Based on Investigator Assessment in All Participants

  Up to 30 months (through database cut-off date of 26 Oct 2017)

• PFS According to Immune-Related Response Evaluation Criteria in Solid Tumors (irRECIST) Based on BICR in PD-L1 Positive Participants

  Up to 30 months (through database cut-off date of 26 Oct 2017)

Study Arms (2)

Pembrolizumab

EXPERIMENTAL

Participants receive 200 mg intravenous (IV) pembrolizumab on Day 1 of each 21-day cycle, for up to 35 administrations (approximately 2 years).

Biological: pembrolizumab

Paclitaxel

ACTIVE COMPARATOR

Participants receive 80 mg/m\^2 IV paclitaxel on Days 1, 8, and 15 of each 28-day cycle, until disease progression or unacceptable toxicity.

Drug: paclitaxel

Interventions

pembrolizumab BIOLOGICAL

200 mg administered as IV infusion on Day 1 of each 21-day cycle.

Also known as: MK-3475

Pembrolizumab

paclitaxel DRUG

80 mg/m\^2 administered as IV infusion on Days 1, 8, and 15 of each 28-day cycle.

Also known as: TAXOL®

Paclitaxel

Eligibility Criteria

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

You may qualify if:

• Histologically- or cytologically-confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
• Confirmed metastatic or locally advanced, unresectable disease (by computed tomography \[CT\] scan or clinical evidence)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Progression on or after prior first-line therapy containing any platinum/fluoropyrimidine doublet
• Willing to provide tumor tissue for PD-L1 biomarker analysis (new or archived specimens with agreement of Sponsor). As of 20 March 2016, participants must be PD-L1 positive to be enrolled.
• Human epidermal growth factor receptor 2 (HER-2/neu) status known and participants with HER2/neu positive tumors show documentation of disease progression on treatment containing trastuzumab
• Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
• Male participants should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of pembrolizumab or through 180 days after the last dose of paclitaxel.
• Adequate organ function

You may not qualify if:

• Currently participating and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigation device within 4 weeks of the first dose of medication
• Squamous cell or undifferentiated gastric cancer
• Active autoimmune disease that has required systemic treatment in past 2 years (replacement therapy is not considered a form of systemic treatment
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or not recovered from AEs due to agents administered more than 4 weeks earlier
• Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or not recovered from adverse events due to a previously administered agent or surgery
• 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, or in situ cervical cancer that has undergone potentially curative therapy)
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis
• History of (noninfectious) pneumonitis that required steroids or current pneumonitis
• Active infection requiring systemic therapy
• Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Pregnant or 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 pembrolizumab or through 180 days after the last dose of paclitaxel.
• Prior immunotherapy including anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or previously participated in Merck pembrolizumab (MK-3475) clinical trial
• Known history of human immunodeficiency virus (HIV)
• Known active Hepatitis B or Hepatitis C

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (8)

• 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

• Shitara K, Di Bartolomeo M, Mandala M, Ryu MH, Caglevic C, Olesinski T, Chung HC, Muro K, Goekkurt E, McDermott RS, Mansoor W, Wainberg ZA, Shih CS, Kobie J, Nebozhyn M, Cristescu R, Cao ZA, Loboda A, Ozguroglu M. Association between gene expression signatures and clinical outcomes of pembrolizumab versus paclitaxel in advanced gastric cancer: exploratory analysis from the randomized, controlled, phase III KEYNOTE-061 trial. J Immunother Cancer. 2023 Jun;11(6):e006920. doi: 10.1136/jitc-2023-006920.

  PMID: 37399357 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

• Cristescu R, Aurora-Garg D, Albright A, Xu L, Liu XQ, Loboda A, Lang L, Jin F, Rubin EH, Snyder A, Lunceford J. Tumor mutational burden predicts the efficacy of pembrolizumab monotherapy: a pan-tumor retrospective analysis of participants with advanced solid tumors. J Immunother Cancer. 2022 Jan;10(1):e003091. doi: 10.1136/jitc-2021-003091.

  PMID: 35101941 DERIVED

• Fuchs CS, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. doi: 10.1007/s10120-021-01227-z. Epub 2021 Sep 1.

  PMID: 34468869 DERIVED

• Van Cutsem E, Amonkar M, Fuchs CS, Alsina M, Ozguroglu M, Bang YJ, Chung HC, Muro K, Goekkurt E, Benson AB 3rd, Sun W, Wainberg ZA, Norquist JM, Chen X, Shih CS, Shitara K. Health-related quality of life in advanced gastric/gastroesophageal junction cancer with second-line pembrolizumab in KEYNOTE-061. Gastric Cancer. 2021 Nov;24(6):1330-1340. doi: 10.1007/s10120-021-01200-w. Epub 2021 Aug 7.

  PMID: 34363528 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, Ozguroglu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. doi: 10.1016/S0140-6736(18)31257-1. Epub 2018 Jun 4.

  PMID: 29880231 DERIVED

Related Links

• Merck Oncology Clinical Trials Information

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

pembrolizumab; Paclitaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 23, 2015
• First Posted: February 25, 2015
• Study Start: May 11, 2015
• Primary Completion: October 26, 2017
• Study Completion: June 10, 2021
• Last Updated: June 6, 2022
• Results First Posted: November 20, 2018

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will share