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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)

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ClinicalTrials.gov Identifier: NCT02494583
Recruitment Status : Active, not recruiting
First Posted : July 10, 2015
Last Update Posted : April 25, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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 will be randomly assigned to one of the three treatment arms of the study: pembrolizumab as monotherapy, or pembrolizumab + cisplatin + 5-fluorouracil (5-FU) or capecitabine, or placebo + cisplatin + 5-FU or capecitabine. The primary study hypotheses are that pembrolizumab in combination with chemotherapy is superior to chemotherapy alone in terms of Progression-free Survival (PFS) and Overall Survival (OS) in participants with programmed death-ligand 1 (PD-L1) Combined Positive Score (CPS) ≥1 and that pembrolizumab combination with chemotherapy is superior to chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥10. Primary study hypotheses also are that pembrolizumab monotherapy non-inferior to chemotherapy alone in terms of OS in participants PD-L1 CPS ≥1 and is superior to chemotherapy alone in terms of OS in participants with PD-L1 CPS ≥1 and in participants with PD-L1 CPS ≥10.

Condition or disease Intervention/treatment Phase
Gastric Adenocarcinoma Biological: pembrolizumab Drug: cisplatin Drug: 5-FU Drug: capecitabine Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 764 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Active-Controlled, Partially Blinded, Biomarker Select, Phase III Clinical Trial of Pembrolizumab as Monotherapy and in Combination With Cisplatin+5-Fluorouracil Versus Placebo+Cisplatin+5-Fluorouracil as First-Line Treatment in Subjects With Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma
Actual Study Start Date : July 31, 2015
Estimated Primary Completion Date : February 5, 2019
Estimated Study Completion Date : June 6, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pembrolizumab monotherapy
Participants receive pembrolizumab 200 mg, intravenously (IV) on Day 1 of each 3 week cycle (Q3W)
Biological: pembrolizumab
IV infusion
Other Name: MK-3475

Experimental: Pembrolizumab + cisplatin + 5-FU
Participants receive pembrolizumab 200 mg Q3W + cisplatin 80 mg/m^2 Q3W + 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.
Biological: pembrolizumab
IV infusion
Other Name: MK-3475

Drug: cisplatin
IV infusion

Drug: 5-FU
IV infusion

Drug: capecitabine
oral tablet

Active Comparator: Placebo + cisplatin + 5-FU
Participants receive placebo, IV, Q3W + cisplatin 80 mg/m^2 Q3W + 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
IV infusion

Drug: 5-FU
IV infusion

Drug: capecitabine
oral tablet




Primary Outcome Measures :
  1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by Blinded Independent Central Radiologists' (BICR) Review in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to 44 months ]
  2. Overall Survival (OS) in Participants With PD-L1 CPS ≥1 and in Participants With PD-L1 CPS ≥10 [ Time Frame: Up to 44 months ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) per RECIST 1.1 by BICR Review in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to 44 months ]
  2. Duration of Response (DOR) per RECIST 1.1 by BICR Review in Participants With PD-L1 CPS ≥1 [ Time Frame: Up to 44 months ]
  3. PFS per RECIST 1.1 by BICR Review in Participants Treated with Pembrolizumab Monotherapy [ Time Frame: Up to 44 months ]
  4. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) Core 30-question (C30) Score [ Time Frame: Baseline and Cycles 1, 2, 3, 4, 5 and every 2 cycles thereafter for up to a year or until end of treatment, (whichever comes first) and 30 days post-treatment (Up to 13 months) ]
  5. Change from Baseline in EORTC QLQ Module for Gastric Cancer (STO22) Score [ Time Frame: Baseline and Cycles 1, 2, 3, 4, 5 and every 2 cycles thereafter for up to a year or until end of treatment, (whichever comes first) and 30 days post-treatment (Up to 13 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • HER2/neu protein 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

Exclusion Criteria:

  • 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 180 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
  • Received a live vaccine within 30 days prior to the first dose of study medication

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02494583


Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
Study Director: Medical Director Merck Sharp & Dohme Corp.

Additional Information:
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT02494583     History of Changes
Other Study ID Numbers: 3475-062
2015-000972-88 ( EudraCT Number )
163187 ( Registry Identifier: JAPIC-CTI )
MK-3475-062 ( Other Identifier: Merck Protocol Number )
First Posted: July 10, 2015    Key Record Dates
Last Update Posted: April 25, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Merck Sharp & Dohme Corp.:
Gastric carcinoma
Gastric cancer
Gastroesophageal junction cancer
Gastroesophageal junction carcinoma
PD1
PD-1
PDL1
PD-L1

Additional relevant MeSH terms:
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Cisplatin
Capecitabine
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action