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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 3INTERVENTIONAL

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

A Multicenter, Randomised, Comparative, Open-label Phase III Aiming to Compare the Survival of Patients With Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas Treated by a Combination of Immune Checkpoint Inhibitors (Botensilimab + Balstilimab) Versus the Standard of Care (FOLFOX/XELOX + Nivolumab)

Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas (NCT06346197) is a Phase 3 interventional studying Gastric Cancer and MSI-H, sponsored by Centre Leon Berard. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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).

What Stage of Research Is This?

Phase 3 trials confirm efficacy and safety in large patient groups (often 300–3,000+) and form the evidence base for an FDA approval submission. For Gastric Cancer, Phase 3 studies typically randomize participants between the investigational treatment and either a placebo or current standard of care. A successful Phase 3 result is the threshold most treatments need to clear before regulatory approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 132 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Gastric Cancer subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

Who May Qualify: - Male or female patient ≥18 years of age at time of willing to sign a consent form 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) platelet count at least 100 109/L (without transfusion for platelets within 7 d) blood count (hemoglobin) at least 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) ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
Inclusion Criteria: * 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: 1. ≥ 50 years of age and has not had menses for greater than 1 year. 2. 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. 3. Status is post-hysterectomy, bilateral oophorectomy, or tubal ligation. * Male patients with a female partner(s) of childbearing potential must agree to use highly effective contraceptive measures throughout the study starting with the screening visit through 6 months after the end of the treatment with oxaliplatine or 3 months after the last dose for other study treatments is received. Males with pregnant partners must agree to use a condom; no additional method of contraception is required for the pregnant partner. * Patient should understand, sign, and date the written voluntary informed consent form prior to any protocol-specific procedures performed and should be able and willing to comply with study visits and procedures as per protocol. * Patients must be covered by a medical insurance. Exclusion Criteria: * 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. * Active autoimmune disease or history of autoimmune disease that required systemic treatment within 2 years of the start of study treatment (i.e., with use of disease-modifying agents or immunosuppressive drugs). * History or current evidence of any condition, co-morbidity, therapy, any active infections, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator. * Patients with documented: * Active hepatitis B (chronic or acute; defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) unless their HBV is stably controlled on nucleoside analogs (eg entecavir or tenofovir) which will be continued for the duration of the study. Note: Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as the presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. HBV DNA test must be performed in these patients prior to C1D1. * Active hepatitis C. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA, or * HIV infection * Prior organ or bone marrow transplant. * Pregnant or lactating women.

Treatments Being Tested

DRUG

Balstilimab

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

DRUG

Botensilimab

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

DRUG

Folfox Protocol

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.

DRUG

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

Nivolumab

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

Locations (7)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

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

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06346197), the sponsor (Centre Leon Berard), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06346197 clinical trial studying?

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). The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06346197?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06346197?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06346197. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06346197. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.