HER2 negative, previously untreated, unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma MedDRA version: 21.1 Level: LLT Classification code 10071114 Term: Metastatic gastric adenocarcinoma System Organ Class: 100000004864 MedDRA version: 21.0 Level: LLT Classification code 10058526 Term: Oesophageal adenocarcinoma metastatic System Organ Class: 100000004864
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically- or cytologically-confirmed diagnosis of locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma, with known PD-L1 expression status. 2. Has HER2 negative cancer. HER2 negative is defined as: IHC (0, or 1+) or fluorescence in situ hybridization (FISH) negative (HER2:CEP17 ratio =65 years) yes F.1.3.1 Number of subjects for this age range 1087
Exclusion criteria
Exclusion criteria: 1. Has squamous cell or undifferentiated gastric cancer. 2. Has had 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 intervention. 3. Has pre-existing peripheral neuropathy >Grade 1. 4. Is a WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization or treatment allocation. 5. Has had previous therapy for locally advanced, unresectable and/or metastatic gastric/GEJ cancer. Participants may have received prior neoadjuvant or adjuvant therapy as long as it was completed at least 6 months prior to randomization. 6. 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 co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). 7. Has received prior systemic anticancer therapy including investigational agents within 4 weeks prior to randomization. 8. Has received prior radiotherapy within 2 weeks prior to start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=2 weeks of radiotherapy) to non-central nervous system (CNS) disease. 9. Has received a live vaccine within 30 days prior to the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. 10. 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 intervention. 11. Has a 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 to the first dose of study intervention. 12. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. 13. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention. 14. Has severe hypersensitivity (=Grade 3) to pembrolizumab and/or any of its excipients. 15. Has an active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 16. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. 17. Has an active infection requiring systemic therapy 18. Has a known histor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the overall survival (OS) of the participants following administration of pembrolizumab versus placebo when each is combined with chemotherapy To compare the progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), as assessed by blinded independent central review (BICR), following administration of pembrolizumab versus placebo when each is combined with chemotherapy;Secondary Objective: To compare the objective response rate (ORR) per RECIST 1.1, as assessed by BICR, following administration of pembrolizumab versus placebo when each is combined with chemotherapy To compare the duration of response (DOR) per RECIST 1.1, as assessed by BICR, following administration of pembrolizumab versus placebo when each is combined with chemotherapy in all participants and in participants with PD-L1-positive tumors (CPS =1) To evaluate the safety and tolerability of pembrolizumab plus chemotherapy versus placebo plus chemotherapy ;Primary end point(s): - Overall survival (OS), defined as the time from randomisation to death due to any cause - Progression-free Survival (PFS), defined as the time from randomisation to the first documented disease progression or death due to any cause, whichever occurs first;Timepoint(s) of evaluation of this end point: Overall survival (OS) = time from randomization to death due to any cause; Progression-free survival (PFS) = time from randomization to the first documented disease progression per RECIST 1.1 by (blinded independent central review (BICR) or death due to any cause, whicherver occurs first | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Objective response (OR), defined as Complete response (CR) or partial response (PR) - Duration of Response (DOR), defined as the time from first response (CR or PR) to subsequent disease progression, or death from any cause, whichever occurs first ;Timepoint(s) of evaluation of this end point: - Objective Response Rate (ORR) = proportion of participants who have an overall response – complete response (CR) or partial response (PR); - Duration of Response (DOR) =time from first response (CR or PR) to subsequent disease progression or death from any cause, whichever occurs first | — |
Countries
Australia, Brazil, Canada, Chile, China, Colombia, Denmark, France, Guatemala, Hong Kong, Hungary, Ireland, Israel, Japan, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Russian Federation, South Africa, Spain, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactGlobal Clinical Trial Operations
Merck Sharp & Dohme Limited
Outcome results
None listed