Combining EXL01 with Nivolumab for Advanced Lung Cancer

EXL01 in Combination With Nivolumab for Advanced NSCLC Refractory to Immunotherapy

This study is testing if combining a gut bacteria treatment with an immunotherapy drug can help people with advanced lung cancer who haven't had success with other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 21 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Lille (other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation, prednisone, nivolumab
• Locations: 1 site (Lille)
• Trial ID: NCT06448572 on ClinicalTrials.gov

What this trial studies

This trial investigates the combination of EXL01, a single-strain bacterium from the healthy gut microbiota, with nivolumab, an immunotherapy drug, for patients with advanced non-small cell lung cancer (NSCLC) who have not responded to standard treatments. It is a pilot Phase I/II, one-arm, monocentric study aimed at evaluating the safety and efficacy of this combination therapy. The study targets patients who have progressed after receiving anti-PD-(L)1 agents and platinum-based chemotherapy, focusing on those with limited treatment options. The goal is to assess whether this novel combination can provide clinical benefit in a challenging patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with inoperable advanced or metastatic NSCLC who have previously received anti-PD(L)1 therapy and platinum-based chemotherapy.

Not a fit: Patients with specific oncogene alterations such as EGFR, ALK, ROS1, MET, HER2, or RET mutations may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could offer a new treatment option for patients with advanced NSCLC who have exhausted standard therapies.

How similar studies have performed: While the combination of immunotherapy and microbiota modulation is a novel approach, similar studies have shown promise in enhancing the efficacy of cancer treatments.

Eligibility criteria

Key inclusion Criteria:

1. Patients (male or female) ≥18 years old.
2. ECOG Performance status (PS) 0-1 (WHO).
3. Histologically or cytologically documented inoperable advanced/metastatic NSCLC. (inoperable stage III not amenable to radiation therapy or surgery, stage IV)
4. 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.
5. 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.
6. Must have progressed within 6 months after first dose of anti-PD(L)1 given either alone or in combination with platinum-based chemotherapy.
7. Must have received all validated available standard therapies.
8. Measurable disease according to iRECIST 1.1.
9. Adequate hematological, 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)

Key exclusion Criteria:

1. Small cell lung cancer or tumors with mixed histology including a SCLC component.
2. 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.
3. 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.
4. Living attenuated vaccine received within the 30 previous days.
5. Has received Fecal Microbiota Transplantation within 3 months prior to Screening.
6. 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.
7. History of severe immune-mediated toxicity (≥ grade 3) under immunotherapy treatment.
8. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Where this trial is running

Lille

• CHU Lille — Lille, France (RECRUITING)

Conditions: Non-Small Cell Lung Cancer, Immunotherapy, microbiota, Lung Cancer bacteria, Faecalibacterium prausnitzii