Advanced Gastric or Gastroesophageal Junction Adenocarcinoma
Conditions
Interventions
- Experimental: Pembrolizumab, Cisplatin + 5-FU (FP) or Capecitabine + Oxaliplatin (CAPOX) or S-1 + Oxaliplatin (SOX) , Trastuzumab
- Active Comparator: Placebo, FP or CAPOX or SOX, Trastuzumab
- Dosa
Sponsors
MSD K.K.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic HER2 positive gastric or GEJ adenocarcinoma. 2) HER2-positive defined as either IHC 3+ or IHC 2+ in combination with ISH+ (or FISH), as assessed by central review on primary or metastatic tumor. 3) Have measurable disease as defined by RECIST 1.1 as determined by the site investigator. 4) Male participants must agree to use approved contraception. 5) Female participants who are not pregnant or breastfeeding, and who are either not a woman of childbearing potential (WOCBP), or are a WOCBP who agrees to use approved contraception. 6) Has a performance status of 0 or 1 on the ECOG Performance Scale within 3 days prior to the first dose of trial treatment. 7) Has a life expectancy of greater than 6 months. 8) Has adequate organ function.
Exclusion criteria
Exclusion criteria: 1) Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ 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 treatment. 3) Has had radiotherapy within 14 days of randomization. 4) Has a known additional malignancy that is progressing or has required active treatment within the past 5 years. 5) Has known active CNS metastases and/or carcinomatous meningitis. 6) Has an active autoimmune disease that has required systemic treatment in past 2 years. 7) Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. 8) Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 9) Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis). 10) Has an active infection requiring systemic therapy. 11) Has poorly controlled diarrhea. 12) Accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment. If the participant is receiving diuretic drugs for other reasons, it is acceptable. 13) Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. 14) Has peripheral neuropathy > Grade 1. 15) Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial. 16) A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation. 17) Has active or clinically significant cardiac disease. 18) Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). 19) Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. 20) Has severe hypersensitivity (>=Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products. 21) Has had an allogeneic tissue/solid organ transplant. 22) 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy - To compare progression-free survival (PFS) between treatment groups. - To compare overall survival (OS) between treatment groups. | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy - Objective Response (Complete response (CR) or partial response (PR)): To compare Objective Response Rate (ORR) between treatment groups. - DOR (For participants who demonstrate CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.): To estimate Duration of Response (DOR), per RECIST 1.1 as assessed by BICR for each treatment group. Safety - Adverse events, Discontinuation of study treatment due to AEs: To assess the safety and tolerability of pembrolizumab in combination with trastuzumab plus chemotherapy by proportion of adverse events (AEs) | — |
Countries
Africa, Asia except Japan, Europe, Japan, North America, Oceania, South America
Contacts
Public ContactMSDJRCT inquiry mailbox
MSD K.K.
Outcome results
None listed