Pembrolizumab/Placebo Plus Trastuzumab Plus Chemotherapy in HER2 Positive Advanced Gastric or GEJ Adenocarcinoma
- Conditions
- Gastric or gastroesophageal junction (GEJ) adenocarcinomaMedDRA version: 21.1Level: LLTClassification code: 10071114Term: Metastatic gastric adenocarcinoma Class: 10029104MedDRA version: 21.1Level: LLTClassification code: 10066354Term: Adenocarcinoma of the gastroesophageal junction Class: 10029104Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-508253-98-00
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 745
Histologically or cytologically confirmed diagnosis of previously untreated, locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2) positive gastric or gastroesophageal junction (GEJ) adenocarcinoma, HER2-positive defined as either immunohistochemistry (IHC) 3+ or IHC 2+ in combination with in-situ hybridization positive (ISH+) or fluorescent in-situ hybridization (FISH), as assessed by central review on primary or metastatic tumor, Has measurable disease as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the site investigator, 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, Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale within 3 days prior to the first dose of trial treatment, Has a life expectancy of greater than 6 months, Has adequate organ function
Has had previous therapy for locally advanced unresectable or metastatic gastric/GEJ cancer, Has an active infection requiring systemic therapy, Has poorly controlled diarrhea, 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, 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, Has peripheral neuropathy > Grade 1, Has a known psychiatric or substance abuse disorder that would interfere with cooperation with the requirements of the trial, A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation, Has active or clinically significant cardiac disease, Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies), 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, 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, Has severe hypersensitivity (=Grade 3) to pembrolizumab, trastuzumab, study chemotherapy agents and/or to any excipients, murine proteins, or platinum-containing products, Has had an allogeneic tissue/solid organ transplant, Has received prior therapy with an anti-programmed cell death1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-programmed cell death-ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, Cluster of Differentiation 137 [CD137]), Has had radiotherapy within 14 days of randomization, Has a known additional malignancy that is progressing or has required active treatment within the past 5 years, Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis, Has an active autoimmune disease that has required systemic treatment in past 2 years, Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy, Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis, Has a known history of active tuberculosis (TB; Mycobacterium tuberculosis)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. To compare progression-free survival (PFS) between treatment groups.<br>2. To compare overall survival (OS) between treatment groups.;Secondary Objective: To compare Objective Response Rate (ORR) between treatment groups., To estimate Duration of Response (DOR), per RECIST 1.1 as assessed by BICR for each treatment group., To assess the safety and tolerability of pembrolizumab in combination with trastuzumab plus chemotherapy by proportion of adverse events (AEs);Primary end point(s): Progression-Free Survival (PFS) per RECIST 1.1 assessed by Blinded Independent Central Review (BICR), Overall Survival (OS)
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Objective Response Rate (ORR) per RECIST 1.1 assessed by BICR;Secondary end point(s):Duration of Response (DOR) per RECIST 1.1 assessed by BICR;Secondary end point(s):Number of Participants Who Experience an Adverse Event (AE);Secondary end point(s):Number of Participants Who Discontinue Study Treatment Due to an AE