Ireland
--:--IST
Active, not recruiting Phase 2

TremelImumab aNd Durvalumab For the Non-operatIve Management (NOM) of MSI-high Resectable GC/GEJC.

NCT04817826 · tracked via the Priya Life Science Italy tracker
Phase
Phase 2
Started
2021-04-01
Last updated
2026-09-11

Condition(s) studied

Gastric CancerMicrosatellite Instability

Investigational drug(s) / intervention(s)

Durvalumab →Tremelimumab →

Durvalumab: durvalumab 1500 mg Q4W for 3 cycles (day 1, 29 and 57).

Tremelimumab: tremelimumab 300 mg single administration (day 1)

Study summary

INFINITY is a Phase II, multicentre, single-arm, multi-cohort trial aimed at evaluating the activity and safety of the combination of tremelimumab and durvalumab as neoadjuvant (Cohort 1) and definitive (Cohort 2) treatment for MSI-high gastric/gastroesophageal juction cancer patients eligible for radical surgery.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: 1. Written informed consent and any locally required authorization (such as the European Union \[EU\] Data Privacy Directive) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 2. Age ≥ 18 years old. 3. ECOG Performance Status 0-1. 4. Body weight \>30 kg. 5. Diagnosis of resectable gastric or gastroesophageal junction (Siewert II-III) cancer, categorized according to TNM classification 8th edition: * cT ≥ 2, any cN, M0 * Any cT, cN1-3, M0 6. Absence of distant metastases as defined by negativity of computed tomography (CT) and 18-fluorodeoxyglucose positron-emission tomography (18-FDG PET). 7. Life expectancy of at least 12 weeks 8. MSI-high status confirmed by IHC and multiplex PCR, and EBV-negative status by ISH, as determined centrally at the Co-ordinating Centre. Lack of heterogeneity of dMMR status as showed by lack of tumor cells showing concomitant expression of all 4 protein markers. 9. Adequate bone marrow and organ function, as defined by laboratory tests: 1. Neutrophil count ≥ 1.5 x 10\^3/μL 2. Platelet count ≥ 100 x 10\^6/μL 3. Haemoglobin ≥ 9 g/dL 4. Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values 5. AST (SGOT) and/or ALT (SGPT) \< 2.5 x ULN 6. Creatinine clearance (calculated according to Cockroft and Gault) \> 40 mL/min or serum creatinine \< 1.5 x ULN. 10. Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating Centre. Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site) 2. Previous enrolment in the present study 3. Participation in another clinical study with an investigational product during the last 12 months 4. Signs of distant metastases. 5. Prior medical treatments or irradiation for gastric cancer. 6. 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. 7. Previous treatments with immune checkpoint inhibitors targeting CTLA4, including tremelimumab, PD-1 or PD-L1, including durvalumab. 8. History of allergy or severe hypersensitivity reaction to monoclonal antibodies. 9. History of autoimmune diseases or history of organ transplantation that require immunosuppressive therapy. The following are exceptions to this criterion: * Patients with vitiligo or alopecia * Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement * Any chronic skin condition that does not require systemic therapy * Patients with celiac disease controlled by diet alone 10. History of active primary immunodeficiency. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA 11. Any condition requiring systemic treatment with corticosteroids at doses equal or superior to 10 mg daily of prednisone or equivalents, or other immunosuppressive drugs within 14 days from the inclusion in the study. The following medications are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) 12. Administration of live vaccines within 4 weeks from the inclusion in the study. Note: Patients, if enrolled, should not receive live vaccine while receiving study drug(s) and up to 30 days after the last dose of study drug(s). 13. History of allogenic organ transplantation 14. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent 15. Women in pregnancy or lactation condition. Women with child-bearing potential or sexually-active men not willing to use adequate contraception during the whole study period. 16. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.

Primary outcome measure(s)

  • Primary outcome of Cohort 1: Pathological complete response (ypT0N0) and negative ctDNA status — From the enrollment of the first patient in Cohort 1 up to 4 months from the enrollment of the last patient in Cohort 1
    Rate of patients (%) achieving both pathological complete response (ypT0N0) and negative ctDNA status after neoadjuvant immunotherapy in the intention-to-treat population of Cohort 1
  • Primary outcome of Cohort 2: 2-year complete response rate — From the enrollment of the first patient in Cohort 2 up to 2 years from the end of pre-operative treatment of the last patient enrolled in Cohort 2
    2-year complete response rate, defined as the absence of macroscopic or microscopic residual disease (locally, regionally and distantly) at radiological examinations, tissue and liquid biopsy, in absence of salvage gastrectomy.

Trial sites (1)

FacilityCityRegionStatus
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano Milan Italy
Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT04817826 on ClinicalTrials.gov ↗ ← All trials in Italy