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
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
162
MaaT033 capsule will be taken orally once a day for a week before every Cemiplimab cycle for the first 6 months of treatment.
CB will be administered 350 mg IV over 30 minutes every 21 days up to 2 years
75mg/m2 at day 1 (d1) every 21 days (q21)
Area Under the Curve (AUC) 5-6 at d1 q21
500mg/m2 at day 1 (d1) q21
10mg/kg at d1 and day 15 (d15) every 28 days (q28)
175mg/m2 at d1 q21 or 80 mg/m2 at d1, day 8 (d8), day 15 q28
1250 or 1000 mg/m2 d1, d8 q21
75 mg/m2 d1 q21 or 33mg/mq d1, d8 q21 q21
25-30 mg/m2 d1, d8 q21
30 mg/50 mg per os 3 days per week (metronomic)
Centre Georges François Leclerc
Dijon, France
NOT_YET_RECRUITINGCHU Grenoble
Grenoble, France
NOT_YET_RECRUITINGHôpital Bichat - Claude Bernard
Paris, France
NOT_YET_RECRUITINGHôpital Foch
Suresnes, France
RECRUITINGCentre Hospitalier Sainte Musse Toulon
Toulon, France
RECRUITINGGustave Roussy
Villejuif, France
RECRUITINGDisease Control Rate (DCR)
Percentage of patients who have not shown disease progression regarding complete response, partial response, stable disease as per RECIST 1.1 criteria. Confirmation of response must be demonstrated with an assessment 4-8 weeks from the initial response assessment.
Time frame: At 12 weeks and confirmation 4-8 weeks from the initial response assessment.
Objective Response Rate (ORR)
Percentage of patients who have not shown disease progression regarding complete response and partial response as per RECIST 1.1 criteria.
Time frame: At 12 months, 24 months, 36 months and 60 months.
Progression free survival (PFS)
The PFS is defined as the time from random assignment to the progression, or death due to any cause, whichever occurs first.
Time frame: At 12 months, 24 months, 36 months and 60 months.
Overall survival (OS)
The OS is defined as the time from random assignment to the date of death due to any cause, or to the date of censoring at the last time the subject was known to be alive.
Time frame: At 12 months, 24 months, 36 months and 60 months.
Duration of response
The DoR is defined as the time from the first confirmed patient response (CR or PR) to disease progression (or death from any cause).
Time frame: At 12 months, 24 months, 36 months and 60 months.
Incidence of AEs
Incidence of AEs will be summarized using the National Cancer Institute-Common Terminology Criteria for AEs (NCI-CTCAE) v5.0. Safety parameters include all SAEs or non-serious adverse events (AEs) and deaths graded using the NCI-CTCAE v5.0 (Common Terminology Criteria for AEs).
Time frame: At end of study, 60 months.
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