NCT04951583

Fecal Microbial Transplantation Non-Small Cell Lung Cancer and Melanoma

Phase II Trial of Fecal Microbial Transplantation in Patients With Advanced Non-Small Cell Lung Cancer and Melanoma Treated With Immune Checkpoint Inhibitors.

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 45 (actual)
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of this study is to assess the anti-tumor activity of FMT administered in combination with ICI therapy.

Detailed description

Immune-checkpoint inhibitors (ICI) now represent the backbone therapy for patients with advanced or unresectable non-small cell lung cancer (NSCLC) and melanoma. With the use of anti-PD-1 (Pembrolizumab), overall survival (OS) is now 45% at two years for patients with metastatic NSCLC with a PD-L1 expression level above 50%. The OS for patients with metastatic melanoma is now 52% at five years with combination therapy of anti-CLTA-4 (Ipilimumab) and anti-PD-1 (Nivolumab). However, only a minority of patients obtain durable responses and current biomarkers are unable to consistently and accurately predict response to ICI. Addressing these unmet needs, the gut microbiome has emerged as a potential biomarker of response to ICI. Modulating the gut microbiome to improve response to ICI is an active area of study. One way to modify the gut microbiome composition is through fecal microbial transplantation (FMT) and pre-clinical studies showed improved effectiveness of ICI when mice received FMT from lung cancer patients responding to ICI. Recently, 2 phase I clinical studies published in Science consolidated these findings, and demonstrated the safety of FMT in patients with melanoma treated with ICI. Building on phase I studies showing that FMT is safe in patients with cancer receiving ICI, and compelling data demonstrating the potential of FMT to reverse ICI resistance, there is a strong rationale to further study the role of FMT in improving ICI efficacy in patients with melanoma and NSCLC treated with ICI in the first-line setting in a phase II study. Our primary objective is to assess the impact of FMT on ICI response and survival. Other goals of this trial are to study the changes in the patient's gut microbiome composition and tumor microenvironment contexture following the combination treatment of ICI and FMT. Efficacy of FMT in terms of response rate and overall survival in patients with metastatic melanoma and uveal melanoma will be studies as part of an exploratory endpoint.

Conditions

• Non Small Cell Lung Cancer Metastatic
• Advanced Melanoma

Interventions

Type	Name	Description
COMBINATION_PRODUCT	FMT + ICI	This study will include 3 cohorts of patients: (1) Patients with advanced or unresectable NSCLC, (2) patients with advanced or unresectable melanoma, and (3) patients with unresectable or advanced uveal melanoma. Patients with NSCLC, melanoma, uveal melanoma and will be analyzed in three separate subgroups given their differing clinical outcomes. Each group will be treated with ICI as per their respective first line options, in combination with investigational FMT capsules.

Timeline

• Start date: 2021-11-16
• Primary completion: 2024-09-01
• Completion: 2025-09-01
• First posted: 2021-07-07
• Last updated: 2024-08-07

Locations

6 sites across 1 country: Canada