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

NCT04817826 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 2020-003440-92
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Gastric Cancer; Microsatellite Instability

Keywords

Durvalumab; Tremelimumab; Non-operative management; Surgery; Gastric cancer; Microsatellite Instability

Outcome Measures

Primary Outcomes (2)

• Primary outcome of Cohort 1: Pathological complete response (ypT0N0) and negative ctDNA status

  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

  From the enrollment of the first patient in Cohort 1 up to 4 months from the enrollment of the last patient in Cohort 1

• Primary outcome of Cohort 2: 2-year complete response rate

  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.

  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

Secondary Outcomes (9)

• Patients' quality of life

  For each Cohort, from the enrollment of the first patient up to 4 months from the last patient starting the pre-operative treatment phase

• Patients' quality of life

  For each Cohort, from the enrollment of the first patient up to 4 months from the last patient starting the pre-operative treatment phase

• Patients' quality of life

  For each Cohort, from the enrollment of the first patient up to 4 months from the last patient starting the pre-operative treatment phase

• 3-year disease-free survival

  For each Cohort, from the enrollment of the first patient up to 3 years from the enrollment of the last patient

• 5-year overall survival

  For each Cohort, from the enrollment of the first patient up to 5 years from the enrollment of the last patient

Study Arms (2)

Cohort 1

EXPERIMENTAL

Pre-operative treatment with tremelimumab 300 mg single administration (day 1) and durvalumab 1500 mg Q4W for 3 cycles (day 1, 29 and 57). Patients in Cohort 1 will undergo standard gastrectomy with D2 lymphadenectomy and then they will be followed by an active follow-up every 12 weeks for two years and then a standard follow-up every six months until the end of the fifth year from surgery.

Drug: Durvalumab; Drug: Tremelimumab

Cohort 2

EXPERIMENTAL

Pre-operative treatment with tremelimumab 300 mg single administration (day 1) and durvalumab 1500 mg Q4W for 3 cycles (day 1, 29 and 57). In Cohort 2, patients with no evidence of complete clinical response will undergo standard gastrectomy with D2 lymphadenectomy and then they will be followed up. Patients with complete clinical response will undergo a non-operative management (NOM) with an active follow-up phase every 12 weeks for two years, followed by standard follow-up every six months until the end of the fifth year. At any time during follow-up, in case of clinical suspicion or confirmation of residual gastric cancer, patients will undergo standard surgery according to the clinical practice at their Centre.

Drug: Durvalumab; Drug: Tremelimumab

Interventions

Durvalumab DRUG

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

Cohort 1; Cohort 2

Tremelimumab DRUG

tremelimumab 300 mg single administration (day 1)

Cohort 1; Cohort 2

Eligibility Criteria

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

You may qualify if:

• 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.
• Age ≥ 18 years old.
• ECOG Performance Status 0-1.
• Body weight \>30 kg.
• 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
• Absence of distant metastases as defined by negativity of computed tomography (CT) and 18-fluorodeoxyglucose positron-emission tomography (18-FDG PET).
• Life expectancy of at least 12 weeks
• 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.
• Adequate bone marrow and organ function, as defined by laboratory tests:
• Neutrophil count ≥ 1.5 x 10\^3/μL
• Platelet count ≥ 100 x 10\^6/μL
• Haemoglobin ≥ 9 g/dL
• Total bilirubin lower than 1.5 time the upper-normal limits (ULN) of the Institutional normal values

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
• Previous enrolment in the present study
• Participation in another clinical study with an investigational product during the last 12 months
• Signs of distant metastases.
• Prior medical treatments or irradiation for gastric cancer.
• 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.
• Previous treatments with immune checkpoint inhibitors targeting CTLA4, including tremelimumab, PD-1 or PD-L1, including durvalumab.
• History of allergy or severe hypersensitivity reaction to monoclonal antibodies.
• 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
• 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
• Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra-articular injection)

Sponsors & Collaborators

• Gruppo Oncologico del Nord-Ovest: lead

Study Sites (1)

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

Milan, 20133, Italy

Location

Related Publications (1)

• Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.

  PMID: 32251400 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms; Microsatellite Instability

Interventions

durvalumab; tremelimumab

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Filippo Pietrantonio, MD

  Fondazione IRCCS - Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Phase II, multicentre, single-arm, multi-cohort trial.

Study Record Dates

• First Submitted: March 11, 2021
• First Posted: March 26, 2021
• Study Start: April 1, 2021
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)