NCT07001618

Oral Pooled Fecal Microbiotherapy (MaaT033) Concomitant to Cemiplimab Versus Best Investigator's Choice in Patients With Resistance to Treatment Due to Antibiotics Uptake With Advanced Non-small Cell Lung Cancer

A Randomized Multicenter Phase II Trial Evaluating Oral Pooled Fecal Microbiotherapy (MaaT033) Concomitant to Cemiplimab (CB) Versus Best Investigator's Choice (BIC) in Resistance to PD-1/PD-L1 Blockade Due to Antibiotics (ATB) Uptake in Patients With Advanced Non-small Cell Lung Cancer (NSCLC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 162 (estimated)
• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of IMMUNOLIFE2 is to overcome primary resistance to immune checkpoint inhibitors (ICIs), such as pembrolizumab or nivolumab used alone or in combination with chemotherapy, observed in patients with advanced non-small cell lung cancer (NSCLC) following antibiotic exposure, which induces intestinal dysbiosis. The reintroduction of immunotherapy with Cemiplimab, combined with oral pooled fecal microbiotherapy (MaaT033), aims to restore gut microbiota and potentially reverse resistance to ICIs. The main objective is to determine whether the combination of MaaT033 and Cemiplimab provides a superior disease control rate compared to the current best investigator's choice as comparator. Patients will be randomized to receive either: * Experimental arm: MaaT033 administered orally for one week prior to each cycle of Cemiplimab, which will be given in hospital care every 3 weeks for 6 months, followed by Cemiplimab alone thereafter; * Control arm: Best investigator's choice

Detailed description

IMMUNOLIFE2 is a randomized Phase II clinical trial multicenter aiming at circumventing primary resistance to ICI observed in patients with advanced NSCLC following ATB uptake in the harmful window using FMT strategy (oral pooled fecal microbiotherapy MaaT033) concomitant to CB. Hence the IMMUNOLIFE2 trial described here is exploring the possibility of an improvement of DCR to CB in patients with ICI resistance due to ATB-induced gut dysbiosis. This will be an outstanding opportunity to explore a therapeutic strategy to surpass ATB mediated resistance but for any cause of intestinal dysbiosis that compromise anti-PD1-based therapy efficacy.

Conditions

• NSCLC (Advanced Non-small Cell Lung Cancer)

Interventions

Type	Name	Description
DRUG	MaaT033 capsule	MaaT033 capsule will be taken orally once a day for a week before every Cemiplimab cycle for the first 6 months of treatment.
DRUG	Cemiplimab	CB will be administered 350 mg IV over 30 minutes every 21 days up to 2 years
DRUG	Cisplatin	75mg/m2 at day 1 (d1) every 21 days (q21)
DRUG	Carboplatine	Area Under the Curve (AUC) 5-6 at d1 q21
DRUG	Pemetrexed (Alimta)	500mg/m2 at day 1 (d1) q21
DRUG	Bevacizumab	10mg/kg at d1 and day 15 (d15) every 28 days (q28)
DRUG	Paclitaxel	175mg/m2 at d1 q21 or 80 mg/m2 at d1, day 8 (d8), day 15 q28
DRUG	gemcitabine	1250 or 1000 mg/m2 d1, d8 q21
DRUG	Docetaxel	75 mg/m2 d1 q21 or 33mg/mq d1, d8 q21 q21
DRUG	Vinorelbine i.v. 25 mg/m²	25-30 mg/m2 d1, d8 q21
DRUG	Vinorelbine oral	30 mg/50 mg per os 3 days per week (metronomic)

Timeline

• Start date: 2025-11-17
• Primary completion: 2030-09-01
• Completion: 2032-09-01
• First posted: 2025-06-03
• Last updated: 2026-04-03

Locations

6 sites across 1 country: France