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

Summary

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.

Conditions

• Advanced Gastric Cancer

Interventions

BIOLOGICAL

Rilvegostomig

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.

BIOLOGICAL

Pembrolizumab

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.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-01

Primary Completion

2030-06-01

Completion

2030-06-01

Countries

• Spain

Study Locations