EXL01 (Faecalibacterium prausnitzii single strain, LBP) for Non-small cell lung cancer | Advanced/metastatic non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- Patients (male or female) ≥18 years old.\n- Obtention of an informed written consent before any specific procedure of the study.\n- Patient affiliated to and covered by social security for standard of care.\n- A female participant is eligible to participate if she is not pregnant or breastfeeding and one of the following applies:. - Not a WOCBP as defined in 7.3.1. OR -A WOCBP who agrees to use a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), prior to the first dose of study treatment until at least 5 months after the last dose of nivolumab or 1 month after last dose of EXL01, which ever comes last. The Investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study treatment. In addition, WOCBP agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during the study and until at least 5 months after the last dose of nivolumab. Note: The Investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk of inclusion of WOCBP with an early undetected pregnancy.\n- A male participant is eligible to participate if he agrees to use a highly effective method of contraception,and refrains from donating sperm for the duration of the study and for at least 5 months after the last dose of Nivolumab or 1 months after the last dose of EXL01, which event comes last, unless confirmed to be azoospermic (vasectomized or secondary to medical cause), or abstains from heterosexual intercourse as his preferred and usual lifestyle (abstinient on a long-term and persistent basis) and agrees to remain abstinent.\n- Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product.\n- ECOG Performance status (PS) 0-1 (WHO).\n- Histologically or cytologically documented inoperable advanced/metastatic NSCLC. (inoperable stage III not amenable to radiation therapy or surgery, stage IV).\n- No alterations of key driver oncogenes including EGFR (mutations), ALK (fusions), ROS1 (fusions), MET (METex14 mutations), HER2 (exon 20 insertions), RET (fusions) or BRAF (V600E mutations). KRAS mutations are allowed.\n- Must have previously received anti-PD(L)1 agent and platinum-based chemotherapy, either concomitantly or sequentially. Last dose to have been administered more than 15 days prior to first dose of study drug.\n- Must have progressed within 6 months after first dose of anti-PD(L)1 given either alone or in combination with platinum-based chemotherapy\n- Must have received all validated available standard therapies.\n- Measurable disease according to iRECIST 1.1.\n- Adequate haematological, renal and liver functions within 72 hours before the first dose of study treatment (Absolute Neutrophil Count ≥ 1500/µL ; Platelets ≥ 100 000/µL; Hemoglobin ≥ 9.0 g/dL; Creatinine Clearance ≥ 50 mL/min; Total Bilirubin ≤ 1.5 x ULN; AST and ALT ≤ 2.5 x ULN (≤ 5 x ULN for participants with liver metastasis))"}

Exclusion criteria

• {"criterion_text":"- Small cell lung cancer or tumors with mixed histology including a SCLC component.\n- Has a known active HBV (defined as HbsAg reactive) or HCV (defined as HCV RNA [qualitative] is detected) infection. Documentation of negative HBV (HbsAg) and HCV (qualitative HCV RNA) tests within 30 days prior to Screening may be used in place of a Screening test.\n- Has known Tuberculosis infection.\n- History of active autoimmune disease including but not limited to rheumatoid polyarthritis, myasthenia, autoimmune hepatitis, systemic Lupus, Wegener's granulomatosis, vascular thrombosis associated with antiphospholipid syndrome, Sjogren’s syndrome with interstitial pulmonary disease, recent Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.\n- Diagnosis of immunodeficiency of is receiving systemic treatment with corticosteroids with greater dose than 10 mg prednisone equivalent daily, within 14 days before initiation of the immunotherapy induction. Inhaled, nasal or topic corticosteroids are allowed.\n- Living attenuated vaccine received within the 30 previous days\n- Has received Fecal Microbiota Transplantation within 3 months prior to Screening.\n- General serious condition such as uncontrolled congestive cardiac failure, uncontrolled cardiac arrythmia, uncontrolled ischemic cardiac disease (unstable angina or history of myocardial infarction within the previous 6 months), history or stroke within the 6 previous months.\n- History of severe immune-mediated toxicity (≥ grade 3) under immunotherapy treatment.\n- History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.\n- Received prior radiotherapy within 1 week of start of study intervention or have had a history of radiation pneumonitis. Note: Participants must have recovered from all radiation-related toxicities and not require corticosteroids.\n- Current probiotics administration, or planned probiotics administration during treatment course (other than EXL01).\n- Had major surgery or significant trauma within 4 weeks before the first dose of study drug\n- Had ongoing or active infection within 2 weeks before the first dose of study drug\n- Active inflammatory intestinal disease (Crohn disease, Hemorrhagic recto-colitis, coeliac disease) or any serious chronic intestinal disease with uncontrolled diarrhea, or other inflammatory disease requiring anti-inflammatory medications.\n- Other contra-indications for anti-PD(L)1 antibodies.\n- Has a known history or newly diagnosed GI parasitic infection within 3 months prior to Screening.\n- have not recovered (ie, > Grade 2 is considered not recovered) from adverse reactions due to previous line of antineoplastic treatment at the time of study entry, with the exception of alopecia.\n- Has a history of hypersensitivity to EXL01 and/or any excipients, as listed in the IB. Has a history of hypersensitivity to EXL01 and/or any excipients, which are listed in the IB, and/or to soybean or soy-containing products.\n- Has a history of hypersensitivity to nivolumab.\n- Has difficulties in swallowing.\n- Has received prohibited medication within 14 days or 5-half-lives (whichever is longer) before the first dose of study drug.\n- Other cancer treated within 3 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma\n- Known symptomatic CNS metastases and/or carcinomatous meningitis. Participants with asymptomatic brain metastases (ie, no neurological symptoms and no requirements for corticosteroids > 10mg/d prednisone equivalent) may participate.\n- Inability to receive study information and to give informed consent\n- Patient unable to have a clinical follow-up due to psychological, familial, social or geographical reasons.\n- Legal incapacity (people in jail), or under supervision (i.e. guardianship or curatorship).\n- Has a systemic infection or other serious infection requiring systemic treatment within 30 days prior to Screening.\n- Has a known history of or newly diagnosed infection with HIV. Documentation of a prior negative HIV test within 6 months prior to Screening may be used in place of a Screening test"}

Primary endpoints

• {"endpoint_text":"- The progression-free survival rate (PFS Rate) at 3 months for the assessment of efficacy, defined as the rate of alive and non-progressive subjects as per iRECIST 1.1 over the study subjects, at 3 months from the inclusion.","definition_or_measurement_approach":"Defined as the rate of alive and non-progressive subjects as per iRECIST 1.1 over the study subjects, at 3 months from the inclusion (assessed by the investigator)."}

Secondary endpoints

• {"endpoint_text":"- The number of Grade ≥ 3 treatment-related AE, using CTCAE, occurring during the first 6 weeks of treatment.","definition_or_measurement_approach":"Number of Grade ≥3 treatment-related adverse events using CTCAE occurring during first 6 weeks."}
• {"endpoint_text":"- The Progression Free Survival, defined as the time from inclusion to the first documented disease progression or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Time from inclusion to first documented disease progression or death due to any cause."}
• {"endpoint_text":"- The ORR (Overall Response Rate) as per iRECIST1.1 for the assessment of efficacy, defined as the rate of confirmed Complete Response (CR) or Partial Response (PR) over the study subjects efficacy responses.","definition_or_measurement_approach":"Rate of confirmed CR or PR per iRECIST 1.1."}
• {"endpoint_text":"- The Overall Survival, defined as the time from inclusion to the date of death due to any cause.","definition_or_measurement_approach":"Time from inclusion to date of death due to any cause."}
• {"endpoint_text":"- The Disease Control Rate, defined as the rate of confirmed Complete Response (CR), or Partial Response (PR), or Stable Disease (SD) over the study subjects efficacy responses.","definition_or_measurement_approach":"Rate of confirmed CR, PR, or SD."}
• {"endpoint_text":"- The Duration of Response, for participants who demonstrate confirmed CR or PR, defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Time from first documented CR or PR until disease progression or death."}
• {"endpoint_text":"- The frequency, type and grade of adverse events, using CTCAE version 5, from the inclusion to the end of the follow-up period, for every patients included.","definition_or_measurement_approach":"Frequency, type and grade of AEs per CTCAE v5 from inclusion to end of follow-up."}
• {"endpoint_text":"- The number of discontinuations of study intervention due to an adverse event.","definition_or_measurement_approach":"Count of participants discontinuing study intervention due to AE."}
• {"endpoint_text":"- The molecular (genomic, metabolic, proteomic) determinants of response or resistance to treatment (PFS at 3 months), using blood samples and/or tumor tissue.","definition_or_measurement_approach":"Identification of molecular determinants using blood and/or tumor tissue correlated with PFS at 3 months."}
• {"endpoint_text":"- The immune and microbial determinants of response or resistance (PFS at 3 months) or tolerability to treatment (number of Grade ≥3 AEs), using blood and stool samples.","definition_or_measurement_approach":"Identification of immune and microbial determinants using blood and stool samples correlated with PFS at 3 months and number of Grade ≥3 AEs."}

France

Earliest CTIS Part Ii Submission Date

19-02-2024

Latest Decision Or Authorization Date

31-07-2025

Processing Time Days

528

Number Of Sites

1

Number Of Participants

21

Primary sponsor

Full Name

Centre Hospitalier Universitaire De Lille

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France

Third parties

• {"country":"France","full_name":"Centre Hospitalier Universitaire De Lille","duties_or_roles":"sponsorDuties codes: 1, 5","organisation_type":"Hospital/Clinic/Other health care facility"}