EXLIBRIS : EXL-01 combined with nivolumab for advanced NSCLC refractory to immunotherapy”

Phase 1

• Conditions: Patients (male or female) =18 years old with histologically or cytologically documented inoperable advanced/metastatic Non-Small-Cell Lung Cancer (NSCLC); MedDRA version: 21.1Level: LLTClassification code: 10029514Term: Non-small cell lung cancer NOS Class: 10029104; Therapeutic area: Phenomena and Processes [G] - Circulatory and Respiratory Physiological Phenomena [G09]

• Registration Number: CTIS2023-505285-28-01
• Lead Sponsor: Centre Hospitalier Universitaire De Lille

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-11-29
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

Patients (male or female) =18 years old., Obtention of an informed written consent before any specific procedure of the study., Patient affiliated to and covered by social security for standard of care., A female participant is eligible to participate if she is not pregnant or breastfeeding. Women of child-bearing potential must 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), during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study interventionand agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period. The length of time required to continue contraception for each study intervention is as follows: for 28 days prior to the first dose of investigational product to 7 months after the final dose of investigational product. Women of child-bearing potential must use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and must agree to continue using such precautions for 7 months after the final dose of investigational product., A male participant is eligible to participate if they agree to use a highly effective method of contraception for 28 days prior to the first dose of investigational product, and for the duration of the study and for at least 7 months after the last dose of Nivolumab and/or EXL01. unless confirmed to be azoospermic (vasectomized or secondary to medical cause), or abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent ona long-term and persistent basis) and agrees to remain abstinent, and refrain from donating sperm, Women of child-bearing potential must have a negative pregnancy test within 24h before administration of investigational product., ECOG Performance status (PS) 0-1 (WHO)., Histologically or cytologically documented inoperable advanced/metastatic NSCLC. (inoperable stage III not amenable to radiation therapy or surgery, stage IV)., 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., 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., Must have progressed within 6 months after first dose of anti-PD(L)1 given either alone or in combination with platinum-based chemotherapy, Must have received all validated available standard therapies., Measurable disease according to iRECIST 1.1., 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

Small cell lung cancer or tumors with mixed histology including a SCLC component., 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., Has known Tuberculosis infection., 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., 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., Living attenuated vaccine received within the 30 previous days, Has received Fecal Microbiota Transplantation within 3 months prior to Screening., 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., History of severe immune-mediated toxicity (= grade 3) under immunotherapy treatment., History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease., 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., Current probiotics administration, or planned probiotics administration during treatment course (other than EXL01)., Had major surgery or significant trauma within 4 weeks before the first dose of study drug, Had ongoing or active infection within 2 weeks before the first dose of study drug, 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., Other contra-indications for anti-PD(L)1 antibodies., Has a known history or newly diagnosed GI parasitic infection within 3 months prior to Screening., 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., 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., Has a history of hypersensitivity to nivolumab., Has difficulties in swallowing., Has received prohibited medication within 14 days or 5-half-lives (whichever is longer) before the first dose of study drug., Other cancer treated within 3 years before inclusion except baso-cellular skin carcinoma or cervical / bladder in situ carcinoma, Known symptomatic CNS metastases and/or carcinomatous meningitis. Participants with asymptomatic brain metastases (ie, no neurological sympt

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified