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

ConditionsGastric CancerMSI-HMetastatic CancerAdvanced Cancer
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorCentre Leon Berard

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Balstilimab

    Drug

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

  • 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.

  • 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.

  • 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.

  • Nivolumab

    Drug

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

Treatment groups

132 Participants
are divided into 2 treatment groups
Group A: Experimental armExperimental treatment 2 interventions
Group B: Standard armActive comparator 3 interventions

Trial outcomes

Primary outcomes

1

Survival of patients

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

Time frame
at least 2 years

Secondary outcomes

1

Progression free survival

Time frame
At least 2 years
2

Objective response rate

Time frame
After 16 weeks of treatment
3

Duration of response

Time frame
At least 2 years
4

Adverse Event description as assessed by CTCAE V5.0

Time frame
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

Other outcomes

1

Gene expression and genomic profile description

RNA Sequencing

Time frame
At Cycle 1 Day1, at Cycle4 Day1, at visit 30 days after the last dose (each cycle is 14 or 21 days)
2

Gene expression and genomic profile description

Whole Exome Sequencing

Time frame
At Cycle 1 Day1, at Cycle4 Day1, at visit 30 days after the last dose (each cycle is 14 or 21 days)
3

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

Multi-immunofluorescence to assess the expression of immune and tumor cells markers such as PDL1, TIGIT, LAG3 on tumor samples collected before and during the treatment

Time frame
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)
4

Value of Tumor mutational Burden (Mutation/ Megabase) on tumor and blood (circulating tumor DNA) during treatment

Time frame
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)

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Centre Leon Berard

Lead sponsor

Agenus Inc.

Collaborator

Source ClinicalTrials.gov
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