A Phase Ib trial to evaluate the safety and efficacy of Fecal Microbial Transplantation (FMT) in combination with Nivolumab in subjects with metastatic or inoperable melanoma, microsatellite instability-high (MSI-H) or mismatch-repair deficient (dMMR) cancer, or Non-Small Cell Lung Cancer (NSCLC)
This study is a Phase I single-center adaptive design study to evaluate the safety and efficacy of FMT in combination with Nivolumab for adult subjects with treatment-refractory or inoperable melanoma, MSH-H, dMMr or NSCLC. FMT will be conducted with fecal capsules, originating from patients that have achieved a durable complete response with immune checkpoint inhibitors. The study will evaluate the safety and efficacy of the combination of FMT with Nivolumab, a human immunoglobulin G4 (IgG4) monoclonal antibody that blocks PD-1 (anti PD-1) treatment and explore different biomarkers.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
42
Cohorts A and B - Patients will receive 30 oral capsules per administration for two consecutive days (Days 1-2) Cohort C - Patients will receive FMT via colonscopy (Day 1), followed the day after by adnistration of 12 oral capsules (Day 2) Combination cycles: 6 combined cycles Q2W of FMT maintenance followed by treatment with anti-PD1. Anti-PD-1 will be administered at least one day and up to 3 days after the FMT. Maintenance of FMT by oral capsules: 12 capsules per administration. Anti PD-1 therapy: A dose of 240 mg Nivolumab will be administrated by intravenous infusion.
Sheba Medical Center
Ramat Gan, Israel
RECRUITINGIncidence of FMT-related Adverse Events
Number of patients with adverse events that emerged post FMT. The AE severity grading scale for the NCI-CTCAE (v5.0) will be used for assessing AE severity
Time frame: 3 years
Overall Response Rate (ORR)
Number of patients with objective responses divided by the total number of evaluable patients, according to imaging studies (RECIST 1.1) and iRECIST
Time frame: 3 years
Changes in immune activation in the gut
Immune activation in gut is defined as a 20% or more increase in cluster of differentiation 68 (CD68) cell counts pre and post FMT
Time frame: 3 years
Changes in immune activation in the tumor
Changes in the relative abundance of different immune cell population (such as the proportion of cluster of differentiation 8 (CD8) and T cell in the tumor pre and post FMT
Time frame: 3 years
Progression-free survival (PFS)
Duration of progression free status evaluated according to imaging studies (RECIST 1.1) and iRECIST.
Time frame: 3 years
To assess Overall survival (OS)
The proportion of patients remaining alive from initiation of study treatment until completion of two year follow-up from End of Treatment (EOT)
Time frame: 3 years
To assess Duration of response (DoR)
Time from initial response to disease progression or death among patients who have experienced a Complete Response (CR) or Partial Response (PR) according to RECIST v1.1
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Time frame: 3 years
Incidence of immune related toxicities induced by anti-PD-1
Number and Grade of immune related Adverse events (irAE) reported that emerged post anti-PD1 treatment
Time frame: 3 years