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)

Ella Therapeutics Ltd1 site in 1 country42 target enrollmentNovember 1, 2020

ConditionsMelanoma Stage IV Unresectable Melanoma NSCLC Stage IV

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Melanoma Stage IV
Sponsor: Ella Therapeutics Ltd
Enrollment: 42
Locations: 1
Primary Endpoint: Incidence of FMT-related Adverse Events
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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)

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

November 1, 2020

End Date

July 1, 2023

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Ella Therapeutics Ltd

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age and gender: 18 and older, all genders
•Signed written informed consent . Participants must be willing to participate in the study and provide written and signed informed consent (ICF) for the study.
•Participants must be willing and able to complete all study specific procedures and visits
•For NSCLC patients Histologically or cytologically confirmed metastatic or locally advanced non-small cell lung cancer not amenable to curative treatment that have a confirmed progression on anti-PD-1/PDL1 therapy:
•Subjects may have had a maximum of one prior line of therapy after failure of anti-PD-1/ Programmed death-ligand 1 (PDL1) therapy Received a platinum based chemotherapy for non-small cell lung cancer; or, Subjects with a documented activating mutation {e.g., against epidermal growth factor receptor (EGFR), against rearranged anaplastic lymphoma kinase (ALK), Proto-oncogene tyrosine-protein kinase (ROS)} must have received the appropriate targeted therapy.
•For Melanoma patients Histologically confirmed unresectable or metastatic melanoma not amenable to curative treatment that have a confirmed progression on anti-PD-1/PD-L1 therapy: a. Subjects may have had a maximum of one prior line of therapy after failure of anti-PD-1/PDL1 therapy b. Subjects with a documented B-Raf (BRAF) mutation must have received the appropriate targeted therapy
•For MSI-H/dMMR patients -Histologically confirmed MSI-H/dMMR metastatic solid tumors including the following indications: colorectal adenocarcinoma, gastric adenocarcinoma, esophageal adenocarcinoma, endometrial carcinoma, ovarian carcinoma, pancreatic ductal adenocarcinoma and urothelial carcinoma that had a confirmed progression on anti-PD-1/PD-L1-based therapy.
•Biopsies Patients must agree to study biopsies at two time points: a. Pretreatment and on treatment gut biopsies. b. Pretreatment and on treatment tumor biopsies.
•Measurable disease by RECIST v1.
•Patient status: a. Eastern Cooperative Oncology Group (ECOG) status of 0-1 b. Liver function: Total bilirubin ≤ 2 Upper limit of normal (ULN), Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) ≤ 2.5 ULN (or \< 5 in case of present liver metastasis) c. Neutrophils ≥ 1,000/mm3, platelets ≥ 100,000/mm3, Hb\>8 g/dL d. Serum creatinine ≤ 1.5 ULN e. International normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time (aPTT) ≤1.5x ULN

Exclusion Criteria

•Medical Conditions :
•1.1 History of chronic or active colitis 1.
•Tumor involvement of the esophagus, stomach, small intestine or colo-rectum. Note: not applicable for patients with MSI-H or dMMR colorectal , gastric or esophageal adenocarcinoma 1.
•Has a current active or a past known additional malignancy within the last 5 years.
•Has an active or a documented history of autoimmune disease that required treatment in the past 2 years.
•Known food allergy to eggs, nuts, peanuts 1.
•Known allergy to neomycin,vancomycin or metronidazole 1.
•Pregnant or breastfeeding women 1.
•Has known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies) 1.9 Has known history of or is positive for hepatitis B or Hepatitis C.
•Prior/Concomitant Therapy and medical procedure 2.1 Has ongoing immune-related adverse effects from previous immunotherapy treatments that are of Grade ≥2, excluding endocrine adverse effects 2.2 Immunosuppressive chronic treatments. Patients treated with Prednisone ≤10mg per day may be included.

Outcomes

Primary Outcomes

Incidence of FMT-related Adverse Events

Time Frame: 3 years

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

Overall Response Rate (ORR)

Time Frame: 3 years

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