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 | Unknown Phase 1

• 1 other identifier: 6735-19
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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)

Conditions

Melanoma Stage IV; Unresectable Melanoma; NSCLC Stage IV

Outcome Measures

Primary Outcomes (2)

• Incidence of FMT-related Adverse Events

  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

  3 years

• Overall Response Rate (ORR)

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

  3 years

Secondary Outcomes (6)

• Changes in immune activation in the gut

  3 years

• Changes in immune activation in the tumor

  3 years

• Progression-free survival (PFS)

  3 years

• To assess Overall survival (OS)

  3 years

• To assess Duration of response (DoR)

  3 years

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Combination treatment: anti PD1 + FMT by capsules

Biological: Fecal Microbial Transplantation by capsules

Interventions

Fecal Microbial Transplantation by capsules BIOLOGICAL

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.

Also known as: Nivolumab

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Diagnosis:
• 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 v1.1.
• 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
• Pregnancy a. Negative urine or serum pregnancy test within 72 hours prior to receiving first dose of study procedure in women of childbearing potential. b. Use of an effective contraceptive method throughout the entire treatment period and up to 6 months after the completion of treatment in both males and females of child bearing potential.

You may not qualify if:

• Medical Conditions :
• History of chronic or active colitis 1.2. 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 1.3. 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 1.6. Known allergy to neomycin,vancomycin or metronidazole 1.7. Pregnant or breastfeeding women 1.8. 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.
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with i.v. antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to the start of Day 1 2.4 Medical condition that requires chronic treatment with antibiotics 2.5 Vaccination with live vaccines within 28 days prior to start of Cycle 1, Day 1.
• Has received major surgery (within 28 days prior to the start of Cycle 1, Day 1), other than for diagnosis. Patient must have recovered from all surgery-related toxicities.
• Patient has a known intolerance to anti-PD-L1 or anti-PD1.
• Prior/Concurrent Clinical Study Experience 3.1 Participation in another clinical trial with anti-neoplastic intervention up to 14 days prior to study entry

Sponsors & Collaborators

• Ella Therapeutics Ltd: lead

Study Sites (1)

Sheba Medical Center

Ramat Gan, Israel

RECRUITING

MeSH Terms

Conditions

Melanoma; Carcinoma, Non-Small-Cell Lung

Interventions

Nivolumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Guy Ben-Betzalel, MD

  Sheba Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elizbeth Tarshish, Msc

CONTACT

+972-504048559; elizabeth@ellatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 13, 2020
• First Posted: August 20, 2020
• Study Start: November 1, 2020
• Primary Completion: July 1, 2022
• Study Completion: July 1, 2023
• Last Updated: August 16, 2021

Record last verified: 2021-08

Locations

IL (1)