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ClinicalTrials.gov ID

NCT07788664

Lead Sponsor

Vall d'Hebron Institute of OncologyOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 2

Enrollment

50Estimated

Last Update Posted

Aug 26, 2026Actual

Start Date

Oct 1, 2026Estimated

Primary Completion Date

Jun 1, 2030Estimated

Completion Date

Jun 1, 2030Estimated

Official Title

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

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.

• Advanced Gastric Cancer

• Rilvegostomig
• Pembrolizumab

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria:

1. 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.

2. Age > 18 years at time of study entry.

3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Body weight >30 kg.

5. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma.

6. Unresectable or metastatic gastric cancer or gastroesophageal junction with no previous systemic therapy for advanced disease.

7. IHC of PD-L1 CPS>=1 and HER2-negative.

8. 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.

9. 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).

10. At least one lesion amenable to biopsy must be present.

11. 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.
    • AST (SGOT)/ALT (SGPT) ≤ 3 × ULN, ≤ 5 × ULN in the case of liver metastasis.
    • Measured creatinine clearance (CL) ≥ 45 mL/minute or Calculated creatinine CL>45 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance.

12. Left ventricle ejection fraction (LVEF) ≥ 50% by echocardiogram or multi-gated acquisition (MUGA) scan (performed at screening; historical assessment within 3 months prior to first dose is acceptable if available).

13. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

14. Patient is willing to comply with the following Reproduction and Contraception guidance:

    Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Refer to Contraception Guidance for definitions of women of childbearing potential and highly effective methods of contraception.

    Female patients of childbearing potential:

    1. Must have negative pregnancy test at screening and prior to each administration of investigational product.
    2. If sexually active with a non-sterilized male partner, must use at least 1 highly effective method of birth control from screening until the required contraception period after the last dose of study treatment received, i.e., 60 days after the last dose of rilvegostomig, 4 months after the last dose of pembrolizumab, or 6 months after the last dose of chemotherapy, as applicable and in accordance with local labeling.
    3. Non-sterilized male partners of female patients of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening until the applicable contraception period after the last fose of study treatment received (i.e., 60 days after the last fose of rilvegostomig, 4 months after the last dose of pembrolizu,ab, or 6 months after the last dose of chemotherapy). Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
    4. Must not breastfeed and must not donate, or retrieve for their own use, ova from screening to 60 days after the last dose of investigational product.

    Non-sterilized male patients who are sexually active with a female partner of childbearing potential:

    1. Non-sterilized male patients who are not abstinent and intend to be sexually active with a female partner of childbearing potential must use a male condom plus spermicide (if not available, a male condom without spermicide is acceptable) from screening until the applicable contraception period after the last dose of stdy treatment received (60 days after livegostomig, 4 monhts after pembroliumab, or 6 months after chemotherapy). Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.
    2. Female partners (of childbearing potential) of a male patient also must use at least 1 highly effective method of contraception (see Contraception Guidance) throughout this period.
    3. Male patients must refrain from fathering a child or donating sperm during the study and for the applicable contraception period after the last dose of study treatment received.

15. As judged by investigator, no contradictions for FOLFOX or CAPOX.

Exclusion Criteria:

1. 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.

2. Non-adenocarcinoma histological subtypes.

3. 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.

4. 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.

5. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria

   1. Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.
   2. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with Rilvegostomig may be included only after consultation with the Study Physician.

6. 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.

7. Palliative radiotherapy with a limited field of radiation within 3 weeks of the first dose of study intervention.

8. 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.

9. 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.

10. History of organ transplant or allogenic stem cell transplant.

11. 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

12. 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.

13. History of leptomeningeal carcinomatosis or central nervous metastases.

14. Known to have tested positive for HIV or active tuberculosis infection.

15. Evidence of any of the following infections:

    1. Hepatitis B infection with anti-HBc IgM positive and/or HBV DNA ≥ 2000 IU/ml. Patients with hepatitis B infection who are anti-HBc total positive and HBV DNA < 2000 IU/mL can be included provided they receive antiviral prophylaxis and are managed for their HBV status.
    2. Active hepatitis C infection defined as: anti-HCV positive with HCV RNA detectable, or anti-HCV positive with HCV RNA undetectable less than 12 weeks following treatment for HCV.

    Patients who are anti-HCV positive with HCV RNA undetectable for least 12 weeks, either due to successful treatment, or spontaneous clearance of HCV infection, are eligible. These patients do not need periodic testing of HCV RNA on study, unless clinically indicated.

16. Any other active or uncontrolled infection requiring systemic treatment that has not resolved by the time of study assignment.

17. Any of the following cardiac conditions as determined by the investigator:

    1. Complex ventricular arrhythmia (such as multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia), which is symptomatic or requires treatment (CTCAE Grade 3).
    2. Symptomatic heart failure (as defined by New York Heart Association class ≥ 3).
    3. Cardiomyopathy of any etiology or history of myocarditis.
    4. Myocardial infarction or unstable angina within the past 6 months.
    5. Uncontrolled hypertension.
    6. Mean resting corrected QT interval > 470 ms, obtained from triplicate ECGs performed at screening.
    7. History of QT prolongation associated with other medications that required discontinuation of that medication.
    8. Congenital long QT syndrome], family history of long QT syndrome, or unexplained sudden death under 40 years of age in first-degree relatives.
    9. History of symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted based on investigator's judgement with cardiologist consultation recommended.
    10. Left ventricular ejection fraction (LVEF) < 50% by echocardiogram or MUGA at screening

18. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

19. Pregnant or breastfeeding or intend to become pregnant during the study.

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

None (Open Label)

Lead Sponsor

Vall d'Hebron Institute of OncologyOTHER

jrodruiguez@unav.es+34948255400

jrodruiguez@unav.es+34948255400