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Gut microbiome intervention with EXL01 in combination with nivolumab and FOLFOX as first-line treatment for patients with PD-L1 CPS ≥5 metastatic gastric cancer: A randomized GERCOR phase II study (BIG)
EU CTIS ID: 2023-506753-38-00
What this study is testing
The primary objective is to assess the objective response rate (ORR) at 4 months of patients with PD-L1 CPS ≥ 5 advanced gastric cancer treated by EXL01 plus nivolumab and FOLFOX(experimental arm) as first-line treatment
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join 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
- Availability of a representative tumor tissue specimen for exploratory translational research; tumor tissue samples, either formalin-fixed paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections (minimum of 20 positively charged slides) from primary or metastatic site must be submitted to the central laboratory,
- Registration in a national health care system (PUMa-Protection Universelle Maladie included.
- Age ≥ 18 years
- Women must not be pregnant, breastfeeding, or expecting to conceive during the study
- Reproductive status: a. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug, b. WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and 5 months (nivolumab), 4 months (oxaliplatin), 6 months (5-FU) or at least 1 month (EXL01) of the patient’s last dose of the study drug, c. Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months (nivolumab, oxaliplatin, or 5-FU) or at least 1 month (EXL01) after the last dose of study treatment. In addition, males must be willing to refrain from sperm donation during this time,
You likely can't join if
- Known HER-2 positive status
- Major surgery within 28 days (4 weeks) prior to first dose of study treatment,
- 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
See the full eligibility criteria
Who can join
- 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
- Availability of a representative tumor tissue specimen for exploratory translational research; tumor tissue samples, either formalin-fixed paraffin-embedded (FFPE) tissue block or unstained tumor tissue sections (minimum of 20 positively charged slides) from primary or metastatic site must be submitted to the central laboratory,
- Registration in a national health care system (PUMa-Protection Universelle Maladie included.
- Age ≥ 18 years
- Women must not be pregnant, breastfeeding, or expecting to conceive during the study
- Reproductive status: a. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to the start of study drug, b. WOCBP must agree to use an adequate method of contraception or birth control for the duration of study treatment and 5 months (nivolumab), 4 months (oxaliplatin), 6 months (5-FU) or at least 1 month (EXL01) of the patient’s last dose of the study drug, c. Males who are fertile and sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of study treatment and 6 months (nivolumab, oxaliplatin, or 5-FU) or at least 1 month (EXL01) after the last dose of study treatment. In addition, males must be willing to refrain from sperm donation during this time,
- Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study
- Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma,
- Expression of PD-L1 with a combined positive score (PD-L1 CPS) ≥5
- No prior systemic cancer treatment given as primary therapy for advanced nonresectable or metastatic disease, NB: 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 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:
- Baseline-corrected QT interval ≤ 450 msec for males and ≤ 470 msec for females,
What rules you out
- Known HER-2 positive status
- Major surgery within 28 days (4 weeks) prior to first dose of study treatment,
- 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
- Prior allogeneic bone marrow transplantation or prior solid organ transplantation
- Fecal microbiota transplant within 3 months prior to screening, Note: Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention.
- Probiotics or prebiotic supplements should be avoided during the study,
- Excessive alcohol intake: moderate consumption, defined as no more than 1 drink per day for women and no more than 2 drinks per day for men, is permitted,
- Known allergy and/or hypersensitivity to any component or excipients of study treatments (nivolumab, EXL01), any other live pro-biotherapeutic product, and/or to soybean or soy-containing products,
- Active brain metastases or known history of leptomeningeal carcinomatosis
- Known history or newly diagnosed GI parasitic infection within 3 months prior to screening, NB: Patients must have recovered adequately from the toxicity and/or complications from the treatment prior to starting study intervention,
- Active or chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and/or human immunodeficiency virus infection (HIV 1/2 antibodies). Participants are eligible if they: - Have controlled HCV load defined as undetectable hepatitis C RNA by PCR either spontaneously or in response to a successful prior course of anti-hepatitis C therapy, - Have received HBV vaccination with only anti-HBs positivity and no clinical signs of hepatitis, - Are HBV surface antigen (HBsAg)- and anti- Hepatitis B core antibody (HBc)+ (i.e., those who have cleared HBV after infection), - Are HBsAg+ with chronic HBV infection (lasting 6 months or longer) and meet conditions below: • HBV DNA viral load <100 IU/mL, • Have normal transaminase values, or, if liver metastases are present, abnormal transaminases, with a result of AST/ALT <3 × ULN, which are not attributable to HBV infection, • Start or maintain antiviral treatment if clinically indicated as per the investigator
- Any (attenuated) live vaccine use within 28 days (4 weeks) prior to randomization, while in the study; live vaccines include, but are not limited to, the following: yellow fever, varicella, shingles, measles, mumps, rubella, tuberculosis, rotavirus, influenza
- Ongoing or concomitant use of the antiviral drug sorivudine or its chemically related analogs, such as brivudine
- Known dihydropyrimidine dehydrogenase deficiency (partial or complete),
- Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of the patient’s safety or study results,
- Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness
- Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent.
- 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,
The study team makes the final eligibility decision.
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.