Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Symptoms and General Pathology

Rare Diseases

Melanoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Microsatellite Instability

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Combination treatment: anti PD1 + FMT by capsules

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.

Fecal Microbial Transplantation by capsules

Elizbeth Tarshish, Msc

Meital Bar

Nili Golan

Guy Ben-Betzalel, MD

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.

Stage I:

Cohort A: Fifteen Melanoma patients will be treated with FMT capsules originating from 5 different donors.

Cohort B: Two NSCLC patients will be treated with FMT capsules originating from 2 different donors.

Cohort C: Three MSI-H or dMMR patients will be treated with FMT via colonoscopy and capsules combined with anti-PD-1 (Nivolumab).

An interim analysis will be conducted following completion of recruitment of 15 patients.

Based on the interim analysis, the abovementioned independent cohorts will be expanded to include additional patients as

Stage II:

Cohort A expansion will include 15 melanoma patients Cohort C expansion will include seven MSI-H or dMMR patients.

Patients will be treated with FMT originating from selected donors, combined with anti-PD-1 (Nivolumab).

A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC

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)

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

Number of patients with objective responses divided by the total number of evaluable patients, according to imaging studies (RECIST 1.1) and iRECIST

Immune activation in gut is defined as a 20% or more increase in cluster of differentiation 68 (CD68) cell counts pre and post FMT

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

Duration of progression free status evaluated according to imaging studies (RECIST 1.1) and iRECIST.

The proportion of patients remaining alive from initiation of study treatment until completion of two year follow-up from End of Treatment (EOT)

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

Number and Grade of immune related Adverse events (irAE) reported that emerged post anti-PD1 treatment

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC	NCT04521075	Melanoma Stage ... Unresectable Me... NSCLC Stage IV	Fecal Microbial...	18 Years -	Ella Therapeutics Ltd
A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC	NCT04521075	Melanoma Stage ... Unresectable Me... NSCLC Stage IV	Fecal Microbial...	18 Years -	Ella Therapeutics Ltd
A Phase Ib Trial to Evaluate the Safety and Efficacy of FMT and Nivolumab in Subjects With Metastatic or Inoperable Melanoma, MSI-H, dMMR or NSCLC	NCT04521075	Melanoma Stage ... Unresectable Me... NSCLC Stage IV	Fecal Microbial...	18 Years -	Ella Therapeutics Ltd

Spots Global Cancer Trial Database for fecal microbial transplantation by capsules