The aim of this study is to assess the anti-tumor activity of FMT administered in combination with ICI therapy.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
45
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.
London Health Sciences Centre
London, Ontario, Canada
DRCC Lakeridge Health
Oshawa, Ontario, Canada
Sunnybrook Health Sciences Centre/Sunnybrook Research Institute
Toronto, Ontario, Canada
Centre hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, Canada
Objective response rate in the NSCLC cohort by RECIST criteria.
Objective Response Rate (ORR) as defined by the proportion of patients with NSCLC whose Best Overall Response (BOR) is either a complete response (CR) or partial response (PR) as assessed by iRECIST, based on RECIST v1.1. BOR is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met.
Time frame: up to 2 years
Progression-free survival at 1 year in the NSCLC cohort by RECIST criteria.
Progression-free survival (PFS) at 1 year as assessed by iRECIST and RECIST. PFS is defined by the proportion of treated subjects remaining progression-free and surviving at 1 year, defined as the time from registration to disease progression or death from any cause. The proportion will be calculated by the Kaplan-Meier estimate, which takes into account censored data.
Time frame: At 3 and 6 months, then at 12 months and up to 2 years
Overall survival at 1 year in the NSCLC cohort assessed by RECIST criteria.
Overall survival (OS) at 1 year as assessed by iRECIST and RECIST radiology, defined by OS will be defined as the time of patient registration to the time of death from any cause. The proportion will be calculated by the Kaplan-Meier estimate, which takes into account censored data.
Time frame: At 3 and 6 months, then at 12 months and up to 2 years
Incidence of treatment-related adverse events (Safety and tolerability)
Safety of administration of FMT in combination with ICI in the Safety Analysis Dataset. The assessment of safety will be based on the incidence of AEs, SAEs, AEs leading to discontinuation, and deaths in the Safety Analysis dataset. Treatment-related adverse events will be graded according to the NCI CTCAE v5.0.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
McGill University Health Center
Montreal, Quebec, Canada
CHU de Québec, Centre intégré en cancérologie (CIC), Hôpital de L'Enfant-Jésus
Québec, Quebec, Canada
Time frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.
Incidence of treatment-related laboratory test abdnomarlities (Safety and tolerability)
Clinical laboratory test abnormalities will be examined. Laboratory values will be graded according to the NCI CTCAE v5.0.
Time frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose.