Actively Recruiting
A Randomized Phase 2 Study of Rilvegostomig with Fluoropyrimidine and Trastuzumab Deruxtecan Versus Trastuzumab, Chemotherapy, and Pembrolizumab for First-Line Treatment of HER2-positive Gastric Cancer
Led by AstraZeneca · Updated on 2026-05-12
840
Participants Needed
289
Research Sites
84 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating the efficacy and safety of rilvegostomig combined with fluoropyrimidine and trastuzumab deruxtecan T-DXd compared to trastuzumab, chemotherapy, and pembrolizumab in patients with HER2-positive locally advanced or metastatic gastric or gastroesophageal junction GEJ adenocarcinoma whose tumors express PD-L1 CPS 1. A separate study arm will assess rilvegostomig combined with trastuzumab and chemotherapy to understand the contribution of each treatment component. This is a Phase 2, randomized, open-label, sponsor-blinded clinical trial conducted globally at about 200-250 sites in approximately 25 countries. Participants will be assigned to one of three treatment groups Arm A receives T-DXd, rilvegostomig, and fluoropyrimidine capecitabine or 5-FU Arm B receives pembrolizumab, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin Arm C receives rilvegostomig, trastuzumab, and chemotherapy 5-FU plus cisplatin or capecitabine plus oxaliplatin. Most drugs are administered by intravenous infusion every three weeks, except capecitabine, which is given orally twice daily. The study compares the effects of these combinations as first-line treatments. Participants will be monitored for up to approximately six years to measure outcomes such as progression-free survival and overall survival. Other assessments include response rates, duration of response, adverse events, pharmacokinetics, immunogenicity, and impact on feeding and side effect burden. The study includes regular evaluations of tumor status using RECIST criteria, organ function, cardiac function, and collection of tumor tissue samples. Safety and treatment effects will be followed closely throughout the study duration.
CONDITIONS
Brief Title
A Phase Ⅲ Study of Rilvegostomig in Combination With Fluoropyrimidine and Trastuzumab Deruxtecan as the First-line Treatment for HER2-positive Gastric Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- HER2 positive for gastric cancer on a tumor biopsy
- PD-L1 combined positive score (CPS) of 1 or higher
- Provide a recent tumor tissue sample adequate for HER2 and PD-L1 testing
- Previously untreated, unresectable, locally advanced or metastatic gastric or GEJ adenocarcinoma
- WHO or ECOG performance status of 0 or 1
- Have measurable target disease based on RECIST v1.1
- Adequate organ and bone marrow function
- Left ventricular ejection fraction (LVEF) of 50% or higher within 28 days before randomization
- Adequate treatment washout period before randomization
You will not qualify if you...
- Lack of physiological integrity of the upper gastrointestinal tract
- Known deficiency of dihydropyrimidine dehydrogenase enzyme
- Contraindication to pembrolizumab, trastuzumab, fluoropyrimidine (5-FU or capecitabine), or platinum (cisplatin or oxaliplatin) treatments
- History of another primary malignancy unless treated with curative intent and no active disease for at least 3 years
- Persistent toxicities from previous anticancer therapy
- Spinal cord compression or brain metastases unless asymptomatic, treated, stable, and not requiring corticosteroids or anticonvulsants
- Uncontrolled infections including tuberculosis and active hepatitis A
- Uncontrolled infections requiring intravenous antibiotics, antivirals, or antifungals
- Recent live attenuated vaccine receipt
- Chronic or active hepatitis B or C infection unless controlled
- Clinically significant cardiac or psychological conditions
- Active or prior autoimmune or inflammatory disorders requiring chronic steroids or immunosuppressive treatment
- History or current interstitial lung disease or pneumonitis or suspected cases not ruled out by imaging
- Lung-specific clinically significant illnesses
- Any active non-infectious skin disease needing systemic treatment
- Pleural effusion, ascites, or pericardial effusion requiring drainage or specific therapies
- History of drug-induced severe skin reactions
- Concurrent anticancer treatments except certain inhibitors
- Recent major surgery or significant trauma or anticipated major surgery during the study
- Use of immunosuppressive medication within 14 days before study intervention
Research Team
A
AstraZeneca Clinical Study Information Center
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