Local and Systemic Immune Modulation by Rilvegostomig (AZD2936) in the Treatment of Advanced Gastric Cancer (RILVE Project)

Conditions

• Advanced Gastric Cancer

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Rilvegostomig — BIOLOGICAL
  Rilvegostomig is a humanized bispecific monoclonal antibody that concurrently targets PD-1 and TIGIT, modulating complementary immune checkpoint pathways to enhance T-cell and natural killer cell-mediated antitumor immune responses. In this study, rilvegostomig is administered intravenously at 750 mg every 3 weeks, initially as monotherapy during a window-of-opportunity cycle and subsequently in combination with standard-of-care chemotherapy, followed by possible maintenance treatment with a fluoropyrimidine.
• Pembrolizumab — BIOLOGICAL
  Pembrolizumab is a humanized monoclonal antibody that selectively inhibits PD-1 signaling, resulting in enhanced antigen-specific T-cell activation. In this study, pembrolizumab is used as the reference therapy and will be administered by intravenous infusion at an approved dose of 200 mg every 3 weeks. Participants will receive one cycle of pembrolizumab monotherapy during the window-of-opportunity phase, followed by pembrolizumab in combination with standard-of-care first-line chemotherapy consisting of either FOLFOX or CAPOX. After completion of combination treatment, pembrolizumab may be continued with fluoropyrimidine maintenance therapy for up to 24 months from the first immunotherapy dose.

Study Details

This is a multicenter, randomized Phase II window-of-opportunity study evaluating rilvegostomig (AZD2936) in patients with treatment-naïve, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with PD-L1 CPS ≥1. Rilvegostomig is a humanized bispecific monoclonal antibody that concurrently targets PD-1 and TIGIT, two immune checkpoint pathways involved in tumor immune suppression. The study is designed to characterize and quantify the local and systemic immunological effects induced by rilvegostomig and to define the biological consequences of dual PD-1/TIGIT blockade during an initial window-of-opportunity phase and subsequent combination treatment. Approximately 50 participants will be randomized to receive either rilvegostomig or pembrolizumab. During the window-of-opportunity phase, participants will receive one cycle of immunotherapy monotherapy. Participants in the experimental arm will receive rilvegostomig 750 mg intravenously on Day 1 of a 21-day cycle. Participants in the control arm will receive pembrolizumab 200 mg intravenously on Day 1 of a 21-day cycle. After the window-of-opportunity phase, participants will continue the assigned immunotherapy in combination with standard-of-care first-line chemotherapy, consisting of either FOLFOX administered every 2 weeks or CAPOX administered every 3 weeks, according to investigator choice and institutional practice. Combination treatment will be administered for up to approximately 8 cycles based on the every-3-week immunotherapy schedule, or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. After completion of combination treatment, participants may continue maintenance therapy with a fluoropyrimidine, either capecitabine or 5-fluorouracil with leucovorin, plus the assigned immunotherapy for up to 24 months from the first immunotherapy dose. The primary objective is to assess changes from baseline to the post-window-of-opportunity biopsy in predefined tumor and peripheral immune biomarkers reflecting immune cell infiltration, activation, and functional modulation induced by rilvegostomig. Tumor tissue and peripheral blood samples will be collected at predefined time points to evaluate local and systemic immune changes, immune cell composition, immune activation markers, immune function, and exploratory biomarkers associated with treatment response. Secondary objectives include assessment of antitumor activity, evaluation of whether immunological changes may serve as biomarkers of treatment response, and characterization of the safety and tolerability of rilvegostomig or pembrolizumab as monotherapy and in combination with FOLFOX or CAPOX. Antitumor activity will be evaluated by radiologic tumor assessments using CT or MRI according to RECIST version 1.1, including objective response rate and progression-free survival. Safety will be monitored throughout the study by assessment of adverse events, serious adverse events, immune-mediated adverse events, dose-limiting toxicities, physical examinations, vital signs, ECOG performance status, clinical laboratory evaluations, and other clinically indicated assessments. The study aims to determine whether rilvegostomig induces a distinct immune modulation profile compared with PD-1 inhibition alone and to support the identification of immune and molecular biomarkers that may inform future therapeutic strategies in advanced gastric cancer.

Key Dates

First listed

Aug 26, 2026

Start date

Oct 1, 2026

Status verified

Jun 2026

Primary completion

Jun 1, 2030

Completion

Jun 1, 2030

Study Design

Enrollment

50 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Rilvegostomig monotherapy
  Participants randomized to the experimental arm will receive rilvegostomig by intravenous infusion. During the window-of-opportunity phase, participants will receive one cycle of rilvegostomig monotherapy at 750 mg on Day 1 of a 21-day cycle. Thereafter, rilvegostomig 750 mg will be administered every 3 weeks in combination with standard-of-care first-line chemotherapy, consisting of either FOLFOX every 2 weeks or CAPOX every 3 weeks, according to investigator choice. Combination treatment will continue for up to approximately 8 cycles based on the every-3-week immunotherapy schedule, or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. After completion of combination therapy, participants may continue maintenance treatment with rilvegostomig plus a fluoropyrimidine for up to 24 months from the first immunotherapy dose.
• Active Comparator: Pembrolizumab monotherapy
  Participants randomized to the control arm will receive pembrolizumab by intravenous infusion. During the window-of-opportunity phase, participants will receive one cycle of pembrolizumab monotherapy at 200 mg on Day 1 of a 21-day cycle. Thereafter, pembrolizumab 200 mg will be administered every 3 weeks in combination with standard-of-care first-line chemotherapy, consisting of either FOLFOX every 2 weeks or CAPOX every 3 weeks, according to investigator choice. Combination treatment will continue for up to approximately 8 cycles based on the every-3-week immunotherapy schedule, or until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. After completion of combination therapy, participants may continue maintenance treatment with pembrolizumab plus a fluoropyrimidine for up to 24 months from the first immunotherapy dose.

Primary Outcome Measure

Change From Baseline in Tumor and Peripheral Immune Biomarkers After Window-of-Opportunity Treatment [ Time Frame: Baseline to Cycle 2 Day 1 (each cycle is 21 days), prior to study treatment dosing on Cycle 2 Day 1. ]

Related Studies

• Phase 1/2 Study of BHB810 in Advanced Gastric and GEJ Adenocarcinoma
  PHASE1/PHASE2 · Recruiting · BigHat Biosciences, Inc. · Fairfax, Virginia