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.
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.
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.
Parallel
Rilvegostomig
Biological/VaccineRilvegostomig 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/VaccinePembrolizumab 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.
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.
Progression-free survival (PFS).
PFS is defined as the time from randomization until radiological progression (per Response Evaluation Criteria in Solid Tumors, Version 1.1 \[RECIST 1.1\]) or death due to any cause (in the absence of progression).
Overall response rate (ORR).
ORR is defined as the proportion of patients who have a confirmed complete response (CR) or confirmed partial response (PR), by using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST 1.1).
Changes in Immune and Tumor Marker Profiles
This outcome will assess the presence of, or changes in, phenotype or expression of predefined immune and tumor markers or profiles in tumor tissue and peripheral blood samples. Analyses may include activated T cells, immune cell receptor repertoires, HLA allotypes, IFN-γ, CD8, tumor-infiltrating lymphocytes, and other immune or tumor microenvironment markers. The assessment is intended to characterize local and systemic immunological changes associated with rilvegostomig treatment and to explore whether these markers may serve as biomarkers of treatment response.
Changes in ctDNA Mutation Profile
This outcome will assess the presence, profile, or change in circulating tumor DNA (ctDNA) mutations in plasma samples to characterize molecular features potentially associated with treatment response, sensitivity, or resistance.
Click on the lead sponsor to view all of their trials.
This trial is not recruiting at the moment. You can still explore other options:
