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

Recruiting now · Phase 3

Conditions studied: Gastric Cancer, MSI-H, Metastatic Cancer, Advanced Cancer

In brief

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).

Key facts

Study ID

NCT06346197

Run by

Centre Leon Berard

People needed

132

Starts

2025-12-08

Expected to finish

2028-05-15

Last updated by the study team

2026-06-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female patient ≥18 years of age at time of informed consent form signature.
• Patient with MSI-H/dMMR, HER2 negativeadvanced or metastatic gastric, gastro-oesophageal junction or oesophageal adenocarcinoma whose tumours express PD-L1 with a combined positive score (CPS) ≥ 5. Note :The claudin 18.2 status must be known and documented before inclusion.
• 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)
• Availability of a representative formalin-fixed paraffin-embedded (FFPE) sample of the primary or metastatic tumor tissue (resection or biopsy) with an associated pathology report must be available. This tumor sample must meet the following quality/quantity control criteria: ≥30 % of tumor cells and a tumor surface area ≥ 5mm2 or biopsiable disease (see next inclusion criteria).
• 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
• 9 months after the end of the treatment with oxaliplatin
• 6 months after the end of the treatment with fluorouracil
• 5 months after the end of the treatment with nivolumab or botensilimab or Balstilimab
• 6 months for capecitabine
• Highly effective contraception is defined in Appendix 03.
• Note Non-childbearing potential is defined as:
• ≥ 50 years of age and has not had menses for greater than 1 year.
• Amenorrheic for ≥ 2 years without a hysterectomy and bilateral oophorectomy and a follicle-stimulating hormone value in the postmenopausal range upon pre-study (screening) evaluation.
• Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation.

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
• Patients with known prolongation QT/QTc interval i.e. QT/QTc interval longer than 450 msec for men and longer than 470 msec for women according to the inclusion ECG.
• 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.
• of ILD or non-infectious pneumonitis requiring glucocorticoids.
• History of allogeneic organ transplant.
• Psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
• Patient with peripheral sensory neuropathy with functional impairment.
• Patients with clinically significant active heart disease or myocardial infarction within 6 months, history of uncontrolled or symptomatic cardiac disease.
• Patient with recent (within 7d before C1D1) or concomitant treatment with brivudine.
• Patient with complete absence of dihydropyrimidine dehydrogenase (DPD) activity (blood uracil level ≥ 150 ng/mL) or partial deficit in DPD (i.e. blood uracil level between ≥ 16 ng/ml and < 150 ng/mL)
• Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) within 14 days or another immunosuppressive medication within 30 days of the first dose of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses (≤ 10 mg daily prednisone equivalent) are permitted in the absence of active autoimmune disease.
• Patient with Live vaccines injection within 4 weeks before C1D1. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever and BCG. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however intranasal influenza vaccines (e.g. Flu-Mist®) are live attenuated vaccines, and are not allowed.

Where it is running

• CHU de Brest — Brest, France (enrolling)
• CHU de Clermont-Ferrand — Clermont-Ferrand, France (enrolling)
• Centre Léon Bérard — Lyon, France (enrolling)
• Hôpital Privé Jean Mermoz — Lyon, France (enrolling)
• Institut Paoli Calmettes — Marseille, France (enrolling)
• Institut Mutualiste Montsouris — Paris, France (enrolling)
• CHU de Poitiers — Poitiers, France (enrolling)

Full record on ClinicalTrials.gov

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