First-line EXL01 With Nivolumab and FOLFOX for PD-L1 CPS ≥5 Metastatic Gastric Cancer

NCT06253611 | Recruiting Phase 2 DMC

• 1 other identifier: BIG G-122 PRODIGE 94
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 37

Brief Summary

This is a randomized non-comparative, multicenter phase II study in patients with PD-L1 PD-L1 combined positive score (CPS) ≥5 advanced gastric cancer to evaluate the efficacy and safety of nivolumab and FOLFOX in combination with EXL01 as first-line treatment. After signing the informed consent form, and upon confirmation of the patient's eligibility, patients will be randomized in a 2:1 ratio to either the nivolumab and FOLFOX plus EXL01 arm (experimental) or the nivolumab and FOLFOX arm (control). In both arms, treatment will be given until PD, unacceptable toxicity or for a maximum of 24 months (52 cycles).

Conditions

Gastric Cancer

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR) at 4 months

  ORR measured at 4 months post randomization in patients with PD-L1 CPS ≥5 advanced gastric cancer treated by first-line EXL01 plus nivolumab and FOLFOX. ORR at 4 months is defined as the number of patients with a CR or PR evaluated by RECIST v 1.1 criteria divided by the number of patients evaluable.

  At 4 months

Secondary Outcomes (7)

• Overall survival (OS)

  Maximum 3 years after randomization

• Progression-free survival (PFS)

  Maximum 3 years after randomization

• Assessment of safety profile

  Maximum 3 years after randomization

• Duration of response (DoR)

  Maximum 3 years after randomization

• Objective response rate (ORR)

  Maximum 3 years after randomization

Study Arms (2)

Nivolumab Combined With FOLFOX and EXL01

EXPERIMENTAL

Nivolumab 240 mg IV q2w and FOLFOX q2w plus EXL01 orally once daily

Drug: Nivolumab; Drug: FOLFOX regimen; Biological: EXL01

Nivolumab and FOLFOX

ACTIVE COMPARATOR

Nivolumab 240 mg IV q2w and FOLFOX q2w

Drug: Nivolumab; Drug: FOLFOX regimen

Interventions

Nivolumab DRUG

Nivolumab 240 mg IV; every 2 weeks

Also known as: Opdivo

Nivolumab Combined With FOLFOX and EXL01; Nivolumab and FOLFOX

FOLFOX regimen DRUG

Oxaliplatin 85 mg/m², leucovorin 400 mg/m², bolus of 5-FU 400 mg/m², continuous 5-FU 2400/m² in 46 hours; every 2 weeks

Also known as: Leucovorin, fluorouracil, and oxaliplatin

Nivolumab Combined With FOLFOX and EXL01; Nivolumab and FOLFOX

EXL01 BIOLOGICAL

Orally 1 capsule/day, starting on day 1 of each FOLFOX/nivolumab treatment.

Nivolumab Combined With FOLFOX and EXL01

Eligibility Criteria

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

You may qualify if:

• Patients must have dated and signed an approved written informed consent form. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
• Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study,
• Target Population
• Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma,
• No prior systemic cancer treatment given as primary therapy for advanced nonresectable or metastatic disease, Note: if patient received neoadjuvant/adjuvant therapy, this therapy should be completed at least 6 months prior to the diagnosis of metastatic or recurrent disease is made. Palliative radiotherapy is allowed and must be completed 2 weeks prior to randomization,
• At least one measurable lesion as assessed by computed tomography (CT)-scan or magnetic resonance imaging (MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 and feasibility of repeated radiological assessments; radiographic tumor assessment should be performed within 28 days prior to randomization,
• Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1,
• Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 14 days prior to randomization of study treatment:
• White blood cell ≥ 2000/μL;
• Neutrophils ≥ 2000/μL;
• Platelets ≥ 100.000/μL;
• Hemoglobin ≥ 9.0 g/dL;
• Serum albumin ≥ 30 g/L;
• Serum creatinine level ≤ 150 μM and calculated creatinine clearance (Cockcroft-Gault) \> 50 mL/minute,
• Total bilirubin ≤ 1.5 x upper normal limit (ULN);

You may not qualify if:

• Target Disease Exceptions
• Active brain metastases or known history of leptomeningeal carcinomatosis,
• Ascites, which cannot be controlled with appropriate interventions,
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast,
• Active, known, or suspected autoimmune disease; type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted,
• Interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected treatment-related pulmonary toxicity,
• Prior treatment with an anti-PD(L)1, anti-LAG-3, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co- stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents,
• Condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days (2 weeks) of randomization. Inhaled or topical steroids, and adrenal replacement steroid doses \>10 mg daily prednisone equivalent, are permitted prior to randomization in the absence of active autoimmune disease,
• Persistence of toxicity (The National Cancer Institute Common Terminology Criteria for Adverse Event \[NCI CTCAE\] v 5.0) grade \>1 related to prior anticancer treatments,
• Major surgery within 28 days (4 weeks) prior to first dose of study treatment, Note: Participants who had surgery \>4 weeks prior to screening must have recovered adequately from any toxicity and/or complications from the surgery or trauma prior to starting study intervention.
• Concomitant unplanned antitumor therapy (e.g., chemotherapy, molecular targeted therapy, radiotherapy, immunotherapy),
• GI obstruction, poor oral intake, or difficulty in taking oral medication or difficulties in swallowing; nasogastric tubes are not permitted,
• Known GI malabsorption,
• Is currently participating in or has participated in a study with an investigational compound within 28 days prior to the first dose of study treatment, Note: Participants who have entered the follow-up phase of an investigational study may participate so long as it has been at least 3 months since the last dose of the previous investigational agent,
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation,

Sponsors & Collaborators

• GERCOR - Multidisciplinary Oncology Cooperative Group: lead

Study Sites (37)

Institut de Cancerologie de L'Ouest Paul Papin

Angers, France

NOT YET RECRUITING

Clinique Sainte Catherine

Avignon, France

RECRUITING

Centre Hospitalier Universitaire Jean Minjoz

Besançon, France

RECRUITING

Institut Bergonie

Bordeaux, France

NOT YET RECRUITING

Centre Hospitalier Universitaire Morvan

Brest, France

NOT YET RECRUITING

Centre Francois Baclesse

Caen, France

NOT YET RECRUITING

Centre Hospitalier de Cholet

Cholet, France

RECRUITING

Centre Hospitalier Universitaire Clermont Ferrand - Site Estaing

Clermont-Ferrand, France

NOT YET RECRUITING

Centre Hospitalier Henri Mondor

Créteil, France

NOT YET RECRUITING

Centre Georges Francois Leclerc

Dijon, France

RECRUITING

Centre Hospitalier Universitaire Grenoble Alpes - Site Nord - Hopital Michallon

La Tronche, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Lille

Lille, France

RECRUITING

Hopital Leon Berard

Lyon, France

RECRUITING

Hopital Prive Jean Mermoz

Lyon, France

NOT YET RECRUITING

Hopital La Timone

Marseille, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Montpellier

Montpellier, France

NOT YET RECRUITING

Centre Hospitalier Universitaire Nantes - Hopital Hotel Dieu

Nantes, France

NOT YET RECRUITING

Centre Antoine Lacassagne

Nice, France

RECRUITING

Centre Hospitalier Cochin

Paris, France

NOT YET RECRUITING

Groupe Hospitalier Diaconesses Croix Saint-Simon

Paris, France

NOT YET RECRUITING

Hopital Europeen Georges Pompidou

Paris, France

NOT YET RECRUITING

Hopital Saint Antoine

Paris, France

RECRUITING

Hopital Saint-Louis

Paris, France

NOT YET RECRUITING

Institut Curie

Paris, France

NOT YET RECRUITING

Institut Gustave Roussy

Paris, France

NOT YET RECRUITING

Institut Mutualiste Montsouris

Paris, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Poitiers - Hopital de La Miletrie

Poitiers, France

RECRUITING

Centre Hospitalier Universitaire Reims Hopital Robert Debre

Reims, France

RECRUITING

Institut Jean Godinot

Reims, France

NOT YET RECRUITING

Centre Hospitalier Universitaire de Rennes

Rennes, France

NOT YET RECRUITING

Hopital D'Instruction Des Armées Bégin

Saint-Mandé, France

NOT YET RECRUITING

Centre Hospitalier Saint-Malo

St-Malo, France

NOT YET RECRUITING

Institut de Cancerologie Strasbourg Europe

Strasbourg, France

NOT YET RECRUITING

Centre Hospitalier Universitaire Tours - Hopital Trousseau

Tours, France

NOT YET RECRUITING

CENTRE HOSPITALIER REGIONAL UNIVERSITAIRE DE NANCY Site Brabois

Vandœuvre-lès-Nancy, France

NOT YET RECRUITING

Hopital Paul Brousse

Villejuif, France

RECRUITING

Medipole Hopital Mutualiste Lyon-Villeurbanne

Villeurbanne, France

NOT YET RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Nivolumab; Folfox protocol; Leucovorin; Fluorouracil; Oxaliplatin

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals

Study Officials

• Romain Cohen, MD

  Saint-Antoine Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marie-Line GARCIA LARNICOL, MD

CONTACT

+33 (01) 40 29 85 04; marie-line.garcia-larnicol@gercor.com.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 31, 2024
• First Posted: February 12, 2024
• Study Start: April 16, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (37)