Fecal Microbial Transplantation Non-Small Cell Lung Cancer and Melanoma (FMT-LUMINATE)
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|ClinicalTrials.gov Identifier: NCT04951583|
Recruitment Status : Not yet recruiting
First Posted : July 7, 2021
Last Update Posted : July 21, 2021
|Condition or disease||Intervention/treatment||Phase|
|Non Small Cell Lung Cancer Metastatic Advanced Melanoma||Combination Product: FMT + ICI||Phase 2|
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 (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||
This is a multi-center single-arm, open-label Simon two-stage, phase II trial in patients with metastatic or unresectable non-small cell lung cancer (NSCLC) and melanoma treated with immune checkpoint inhibition.
Patients will receive standard-of-care immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT).
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Fecal Microbial Transplantation in Patients With Advanced Non-Small Cell Lung Cancer and Melanoma Treated With Immune Checkpoint Inhibitors.|
|Estimated Study Start Date :||September 1, 2021|
|Estimated Primary Completion Date :||September 1, 2024|
|Estimated Study Completion Date :||September 1, 2025|
Experimental: Immune checkpoint inhibitor (ICI) therapy in combination with fecal microbial transplantation (FMT).
Metastatic or advanced NSCLC: Single-agent Pembrolizumab (2 mg/kg or 200 mg every 3 weeks) in combination with investigational FMT capsules as follows: Full FMT at least 7 days prior to first cycle of Pembrolizumab, followed by supportive FMT within 7 days of the second cycle of Pembrolizumab, followed by supportive FMT within 7 days of the third cycle of Pembrolizumab.
Metastatic melanoma and uveal melanoma: Combination therapy of Ipilimumab plus Nivolumab (Ipilimumab 3 mg/kg every 3 weeks and Nivolumab 1 mg/kg every 3 weeks x 4 doses, followed by Nivolumab 3 mg/kg or 240mg every 2 weeks or 6 mg/kg or 480mg every 4 weeks) in combination with investigational FMT capsules as follows: full FMT at least 7 days prior to first treatment with Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the second cycle with combination Ipilimumab plus Nivolumab, followed by supportive FMT within 7 days of the third cycle of Ipilimumab plus Nivolumab.
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.
- Objective response rate in the NSCLC cohort by RECIST criteria. [ Time Frame: up to 2 years ]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.
- Progression-free survival at 1 year in the NSCLC cohort by RECIST criteria. [ Time Frame: At 3 and 6 months, then at 12 months and up to 2 years ]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.
- Overall survival at 1 year in the NSCLC cohort assessed by RECIST criteria. [ Time Frame: At 3 and 6 months, then at 12 months and up to 2 years ]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.
- Incidence of treatment-related adverse events (Safety and tolerability) [ Time Frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose. ]
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.
- Incidence of treatment-related laboratory test abdnomarlities (Safety and tolerability) [ Time Frame: Safety follow-up will be maintained up to 90 days following the administration of the last study-drug dose. ]Clinical laboratory test abnormalities will be examined. Laboratory values will be graded according to the NCI CTCAE v5.0.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04951583
|Contact: Wiam Belkaid, PhDfirstname.lastname@example.org|
|Contact: Arielle Elkrief, MDemail@example.com|
|Centre hospitalier de l'Université de Montréal (CHUM)|
|Montréal, Quebec, Canada, H2X 3E4|
|Contact: Wiam Belkaid, PhD 514-836-3273 firstname.lastname@example.org|
|Contact: Arielle Elkrief, MD|
|Principal Investigator: Bertrand Routy, MD, PhD|
|Principal Investigator:||Bertrand Routy, MD, PhD||CHUM|