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

NCT07788664 | Not Yet Recruiting Phase 2

• 2 other identifiers: VHIO26001 / ESR-25-230092026-525620-23-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

Brief 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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Tumor and Peripheral Immune Biomarkers After Window-of-Opportunity Treatment

  This outcome will assess the change from baseline to the post-window-of-opportunity biopsy in predefined tumor and peripheral immune biomarkers reflecting immune cell infiltration, immune cell activation, and functional modulation induced by rilvegostomig in patients with treatment-naïve, advanced gastric cancer. Analyses will use paired tumor tissue and peripheral blood samples collected at predefined time points to characterize local and systemic immunological effects, including changes in immune cell composition, immune activation markers, immune function, and exploratory biomarkers associated with treatment response. The outcome is intended to define the biological consequences of dual PD-1/TIGIT blockade during the window-of-opportunity phase.

  Baseline to Cycle 2 Day 1 (each cycle is 21 days), prior to study treatment dosing on Cycle 2 Day 1.

Secondary Outcomes (21)

• Progression-free survival (PFS).

  From randomization until radiological disease progression per RECIST 1.1 or death due to any cause, whichever occurs first; assessed by CT/MRI every 8 weeks (±7 days) during treatment and thereafter as applicable until progression; up to 4 years

• Overall response rate (ORR).

  Baseline and every 8 weeks (±7 days) during treatment; CR/PR confirmed at least 4 weeks later. If treatment stops without progression, imaging continues until progression, new anticancer therapy, withdrawal of consent, or death.

• Changes in Immune and Tumor Marker Profiles

  Tumor tissue: baseline and Cycle 2 Day 1. Blood: Cycle 1 Day 1 (baseline), Cycle 1 Day 8, and Day 1 of Cycles 2, 3, 5, 7, and 9. Study cycles for biomarker assessments are 21 days (Q3W immunotherapy schedule).

• Changes in ctDNA Mutation Profile

  Blood: Cycle 1 Day 1 (baseline), Cycle 1 Day 8, and Day 1 of Cycles 2, 3, 5, 7, and 9. Study cycles for biomarker assessments are 21 days (Q3W immunotherapy schedule).

• Changes in Genomic Alteration Profile

  Tumor: baseline and Cycle 2 Day 1. Blood: Cycle 1 Day 1 (baseline), Cycle 1 Day 8, and Day 1 of Cycles 2, 3, 5, 7, and 9. Study cycles for biomarker assessments are 21 days.

Study Arms (2)

Rilvegostomig monotherapy

EXPERIMENTAL

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.

Biological: Rilvegostomig

Pembrolizumab monotherapy

ACTIVE COMPARATOR

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.

Biological: Pembrolizumab

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.

Also known as: AZD2936

Rilvegostomig monotherapy

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.

Also known as: Keytruda

Pembrolizumab monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Written informed consent and any locally required authorization (eg, European Union \[EU\] Data Privacy Directive in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations.
• Age \> 18 years at time of study entry.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Body weight \>30 kg.
• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma.
• Unresectable or metastatic gastric cancer or gastroesophageal junction with no previous systemic therapy for advanced disease.
• IHC of PD-L1 CPS\>=1 and HER2-negative.
• Prior curative intent treatment (surgery and, if given in the adjuvant setting, chemotherapy and/or radiation) is permitted, regardless of time to recurrence, provided that no prior immunotherapy was administered in the curative or perioperative setting.
• At least one lesion that qualifies as a RECIST 1.1 measurable target lesion at baseline. However, patients without measurable lesions, but with evaluable disease, would be accepted (e.g.; those patients with advanced disease with peritoneal metastasis).
• At least one lesion amenable to biopsy must be present.
• Adequate normal organ and marrow function as defined below:
• Haemoglobin ≥9.0 g/dL(5.59 mmol/L) with no blood transfusions (packed red blood cells) within 14 days prior to first dose.
• Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1,500 per mm3), with no growth factor support within 14 days prior to first dose.
• Platelet count ≥ 100 × 109/L (100,000 per mm3) with no platelet transfusions within 14 days prior to first dose.
• Serum bilirubin ≤ 1.5 × ULN in the absence of Gilbert's syndrome, ≤ 3 × ULN if the patient has Gilbert's syndrome.

You may not qualify if:

• Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Non-adenocarcinoma histological subtypes.
• Active or ongoing interstitial lung disease/pneumonitis (of any grade), serious chronic gastrointestinal conditions associated with diarrhoea, primary immunodeficiency, or active non-infectious skin disease (including any grade rash, urticaria, dermatitis, ulceration, or psoriasis) requiring systemic treatment.
• Any severe or uncontrolled systemic diseases which, in the investigator's opinion, makes it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol, including psychiatric illness/social situations and substance abuse.
• Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
• Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Rilvegostomig may be included only after consultation with the Study Physician.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions (e.g., hormone replacement therapy) is acceptable.
• Palliative radiotherapy with a limited field of radiation within 3 weeks of the first dose of study intervention.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of treatment. Intranasal, inhaled, or topical steroids and doses below 10mg/24h or prednisone are allowed.
• Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of IP. Note: Local surgery of isolated lesions for palliative intent is acceptable.
• History of organ transplant or allogenic stem cell transplant.
• Active or prior documented autoimmune disorders or inflammatory disorders requiring chronic systemic treatment with the use of disease-modifying agents, corticosteroids, or immunosuppressive drugs. Patients receiving replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) can be enrolled at the discretion of the investigator. t
• History of another primary malignancy, except for malignancy treated with curative intent and with no known active disease ≥ 3 years before the first dose of study intervention and of low potential risk for recurrence, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy or adequately treated carcinoma in situ without evidence of disease.
• History of leptomeningeal carcinomatosis or central nervous metastases.
• Known to have tested positive for HIV or active tuberculosis infection.

Sponsors & Collaborators

• Vall d'Hebron Institute of Oncology: lead

Study Sites (3)

Hospital Universitari Vall D Hebron

Barcelona, Catalonia, 08035, Spain

Location

Clinica Universidad De Navarra

Madrid, Madrid, 28027, Spain

Location

Clinica Universidad De Navarra

Pamplona, Navarre, 31008, Spain

Location

MeSH Terms

Interventions

pembrolizumab

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: August 26, 2026

Record last verified: 2026-06

Locations

ES (3)