Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas

NCT06346197 | Recruiting Phase 3 DMC

• 1 other identifier: ET23-185
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 6

Brief Summary

CIME is a multicenter, randomised, comparative, open-label phase III study aiming to compare the survival of patients suffering from MSI-H/dMMR locally advanced or metastatic oeasogastric adenocarcinoma treated by a bi-immunotherapy (experimental arm) versus standard current treatment (FOLFOX/XELOX + nivolumab : standard arm).

Conditions

Gastric Cancer; MSI-H; Metastatic Cancer; Advanced Cancer

Outcome Measures

Primary Outcomes (1)

• Survival of patients

  Comparison of survival of patients under Botensilimab + Balstilimab versus the standard of care FOLFOX/XELOX + nivolumab

  at least 2 years

Secondary Outcomes (5)

• Progression free survival

  At least 2 years

• Objective response rate

  After 16 weeks of treatment

• Duration of response

  At least 2 years

• Adverse Event description as assessed by CTCAE V5.0

  from the date of first intake of study drug until 90 days after study drug discontinuation or at time of initiation of a new anti-cancer treatment

• EORTC QLQ C30

  At screening, at Cycle1 Day1 pre dose and every 8 weeks until Week 24 and then every 12 weeks until disease progression (assessed at least 24 months follow up)

Other Outcomes (4)

• Gene expression and genomic profile description

  At Cycle 1 Day1, at Cycle4 Day1, at visit 30 days after the last dose (each cycle is 14 or 21 days)

• Gene expression and genomic profile description

  At Cycle 1 Day1, at Cycle4 Day1, at visit 30 days after the last dose (each cycle is 14 or 21 days)

• Number of tumor samples with modification of tumor microenvironment under study treatments

  Cycle 1 Day pre-dose (before the first treatment administration), Cycle 4 Day 1 (i.e. 42 days after 1st dose), in case of disease progression (assessed up to 24 months after randomisation)

Study Arms (2)

Experimental arm

EXPERIMENTAL

Patients treated with Botensilimab + Balstilimab

Drug: Balstilimab; Drug: Botensilimab

Standard arm

ACTIVE COMPARATOR

o FOLFOX\*, IV, Q2W + Nivolumab 240mg, IV, Q2. \*FOLFOX = oxaliplatin 85 mg/m2 , leucovorin 400 mg/m2 , and fluorouracil 400 mg/m2 administered IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours daily or per local standard on Days 1 and 2 of each treatment cycle, every 2 weeks. Premedication is not usually required in the first cycle. For subsequent cycles, adequate premedication may be administrated per local standard. OR * XELOX\*, IV, Q3W + Nivolumab (360 mg, IV, Q3W). XELOX = Oxaliplatin 130mg/m² IV on Day 1 of each treatment cycle + capecitabine 1000mg/m² orally twice daily on Days 1 to 14 of each treatment cycle, every 3 weeks * Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Drug: Folfox Protocol; Drug: XELOX; Drug: Nivolumab

Interventions

Balstilimab DRUG

Balstilimab: 240mg, IV, Q2W, until disease progression, unacceptable toxicity, patient or investigator decision or up to 2 years.

Experimental arm

Botensilimab DRUG

Botensilimab: 75mg, IV for up to 4 doses, Q6W until disease progression, unacceptable toxicity, patient or investigator decision or up to 2 years.

Experimental arm

Folfox Protocol DRUG

oxaliplatin 85 mg/m2 , leucovorin 400 mg/m2 , and fluorouracil 400 mg/m2 administered IV on Day 1 of each treatment cycle, and fluorouracil 1200 mg/m2 IV continuous infusion over 24 hours daily or per local standard on Days 1 and 2 of each treatment cycle, every 2 weeks.Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Standard arm

XELOX DRUG

Oxaliplatin 130mg/m² IV on Day 1 of each treatment cycle + capecitabine 1000mg/m² orally twice daily on Days 1 to 14 of each treatment cycle, every 3 weeks. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Standard arm

Nivolumab DRUG

240mg, IV, Q2. Treatment is recommended until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Standard arm

Eligibility Criteria

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

You may qualify if:

• Male or female patient ≥18 years of age at time of informed consent form signature.
• Patient to be treated with a first line therapy for locally advanced/metastatic disease.
• No prior treatment with chemotherapy for locally advanced/metastatic disease.
• o Note - adjuvant or neoadjuvant chemotherapy is allowed providing that 6 months have relapsed between completion of adjuvant chemotherapy and recurrence.
• Measurable disease (outside any previous irradiated field within the past 6 months) defined as at least one unidimensional lesion that can be accurately measured as ≥ 10 mm with CT scan according to RECIST V1.1 (Appendix 01).
• Note: Lesions intended to be biopsied should not be defined as target lesions.
• Note: previously irradiated lesions can be selected as target lesion only if recurrence/PD is documented after RT.
• Patient with PS ECOG 0 or 1 (Appendix 02).
• Adequate hematologic and end-organ function, defined by the following laboratory test results:
• Absolute neutrophil count ≥ 1.5 109/L (without growth factor support within 14 d) Platelets ≥ 100 109/L (without transfusion for platelets within 7 d) Hemoglobin ≥ 9 g/dL (without transfusion within 7 d) Creatinine clearance according to CKD-EPI ≥ 30 mL/min/1.73 m2 Serum total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert disease for whom a total serum bilirubin ≤ 3 x ULN is acceptable) ASAT and ALAT ≤ 3 x ULN (or up to 5 x ULN in case of liver metastasis or hepatic infiltration)
• Tumor lesion visible by medical imaging and accessible to repeatable percutaneous or endoscopic sampling that permits core needle biopsy without unacceptable risk of a significant procedural complications, and suitable for retrieval of a minimum of 4 cores with a needle minimum diameter :16-gauge.
• Note 1: Fine needle aspirates, bone biopsies do not satisfy the requirement for tumor tissue.
• Note 2: Tumor lesions used for biopsy should not be lesions used as RECIST 1.1 target lesions unless there are no other lesions suitable for biopsy. If a RECIST target lesion is used for biopsy, the lesion must be ≥ 2 cm in longest diameter.
• Women of childbearing potential (WOCBP) must have a negative serum pregnancy test at the Screening Visit (within 72 hours of first dose of study drugs) and must agree to use highly effective contraceptive measures starting with the Screening Visit through
• months after the end of the treatment with oxaliplatin

You may not qualify if:

• Oesogastric cancer eligible to treatment with curative intent
• Patients previously treated by anti-PD-1, anti-PD-L1, or anti-CTLA-4 or any other immunotherapy
• Patients with surgery or radiotherapy within less than 4 weeks before C1D1
• Patients with persistent AE Grade \>1 related to previous anti-cancer treatment, except alopecia (all grades), laboratory value according to criteria I7.
• Patients with: hypokalemia, hypomagnesemia, hypocalcemia less than normal
• Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases.
• Note: Asymptomatic patients with treated CNS lesions are eligible, provided that all of the following criteria are met:
• Measurable disease, per RECIST v1.1, must be present outside the CNS.
• The patient has no history of intracranial hemorrhage or spinal cord hemorrhage.
• Metastases are limited to the cerebellum or the supratentorial region (i.e., no metastases to the midbrain, pons, medulla, or spinal cord).
• There is no evidence of interim progression between completion of CNS-directed therapy and initiation of study treatment.
• The patient has not undergone stereotactic radiotherapy within 7 days prior to initiation of study treatment, whole-brain radiotherapy within 14 days prior to initiation of study treatment, neurosurgical resection within 21 days prior to initiation of study treatment.
• The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anticonvulsant therapy at a stable dose is permitted. A minimal wash-out period of 10days for corticosteroids is required.
• Patients with other malignancy unless this malignancy is not expected to interfere with the evaluation of study endpoints (basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer), or with no evidence of disease for ≥ 2 years.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.

Sponsors & Collaborators

• Centre Leon Berard: lead
• Agenus Inc.: collaborator

Study Sites (6)

CHU de Brest

Brest, 29000, France

RECRUITING

Centre Léon Bérard

Lyon, 69008, France

RECRUITING

Hôpital Privé Jean Mermoz

Lyon, 69008, France

RECRUITING

Institut Paoli Calmettes

Marseille, 13000, France

RECRUITING

Institut Mutualiste Montsouris

Paris, 75000, France

RECRUITING

CHU de Poitiers

Poitiers, 86000, France

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasm Metastasis

Interventions

balstilimab; Folfox protocol; XELOX; Nivolumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Christelle DE LA FOUCHARDIERE, MD

CONTACT

04 91 22 35 03; delafouchardierec@ipc.unicancer.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2024
• First Posted: April 3, 2024
• Study Start: December 8, 2025
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): May 15, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

FR (6)