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)

Plain English Summary

Combination of Immune Checkpoint in Locally Advanced or Metastatic MSI/dMMR Esogastric Adenocarcinomas is a Phase 3 clinical trial sponsored by Centre Leon Berard studying Gastric Cancer, MSI-H, Metastatic Cancer, Advanced Cancer. This trial tests a new combination of immune checkpoint inhibitors (botensilimab + balstilimab) against the current standard treatment for advanced or metastatic esogastric adenocarcinoma. It is for patients with locally advanced or metastatic MSI/dMMR esogastric adenocarcinoma who have not received prior chemotherapy for this stage of disease. Participation involves receiving either the new combination therapy or the standard treatment (chemotherapy plus nivolumab) and attending regular study visits. The standard of care for this condition typically involves chemotherapy regimens like FOLFOX or XELOX, often combined with nivolumab. The trial aims to enroll 132 participants.

Official 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).

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients aged 18 or older with MSI-H/dMMR, HER2-negative advanced or metastatic gastric, gastro-oesophageal junction, or oesophageal adenocarcinoma. Patients must have tumors that express PD-L1 (CPS ≥ 5) and have measurable disease. Patients cannot have received prior chemotherapy for their advanced/metastatic disease, but prior adjuvant or neoadjuvant chemotherapy is allowed if there was a significant time gap before recurrence. Exclusion criteria include prior treatment with other immunotherapies, recent surgery or radiation, persistent side effects from previous treatments, and certain electrolyte imbalances. This trial is studying Gastric Cancer, MSI-H, Metastatic Cancer, Advanced Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures how long patients live, aiming to see if the new combination therapy helps patients survive longer than the current standard treatment. The specific primary outcome measures are: Survival of patients (at least 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for more effective treatments for esogastric adenocarcinomas with MSI/dMMR, a specific genetic profile that may respond better to certain immunotherapies. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Gastric Cancer, MSI-H, Metastatic Cancer, Advanced Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant market for advanced gastric and related cancers, with a focus on a specific genetic subtype (MSI/dMMR) where immunotherapy has shown promise, potentially indicating a Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if your cancer has the MSI-H/dMMR and HER2-negative markers, and if your PD-L1 expression meets the study criteria. Understand the potential side effects of both the new combination and the standard treatment, and discuss how they will be managed. Be prepared for regular clinic visits for treatment, monitoring, and tests, which may include imaging scans and blood work. This trial is currently recruiting participants. The trial is being conducted at 5 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 132 participants

Interventions

• 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.

Primary Outcomes

• Survival of patients (at least 2 years)

Secondary Outcomes

• 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))

Full Eligibility Criteria

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
* Pa

Trial Locations

• CHU de Brest, Brest, France
• Centre Léon Bérard, Lyon, France
• Hôpital Privé Jean Mermoz, Lyon, France
• Institut Paoli Calmettes, Marseille, France
• CHU de Poitiers, Poitiers, France

Frequently Asked Questions

Related Conditions

• Gastric Cancer
• Gastroesophageal Junction Adenocarcinoma
• Esophageal Adenocarcinoma
• Metastatic Cancer
• Locally Advanced Cancer
• MSI-H Cancer
• dMMR Cancer
• Adenocarcinoma
• Gastrointestinal Cancers
• Oncology

More Gastric Cancer Trials

View all Gastric Cancer clinical trials