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
Participants who are at least 18 years of age on the day of signing informed consent,
All participants must understand spoken and written national language,
Histologically confirmed diagnosis of NSCLC (adenocarcinoma versus squamous cell carcinoma versus others)
Have metastatic or unresectable NSCLC and considered by their physician to be indicated for a new line of immunotherapy.
Immunodeficiency or systemic steroid therapy equivalent to prednisolone >10mg/day or equivalent within 7 days prior to the first dose of trial treatment.
Active ongoing infection requiring ATB treatment.
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years prior to enrollment. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
Gustave Roussy, Cancer Campus, Grand Paris
Lead sponsor
MaaT Pharma
Collaborator
Regeneron Pharmaceuticals
Collaborator