Study of Healthy Donor FMT (hdFMT) and Pembrolizumab in Relapsed/Refractory (R/R) PD-L1 Positive NSCLC

NCT05669846 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 22-078
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to determine if Healthy Donor FMT (hdFMT) improves the body's ability to fight cancer in patients with relapsed/refractory PD-L1 Positive NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

Relapsed; Refractory; Healthy Donor FMT (hdFMT)

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) per RECIST v1.1

  The proportion of patients with objective response (Complete Response (CR) or Partial Response (PR)) to R-FMT and pembrolizumab treatment in PD-1 primary refractory NSCLC as assessed per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

  Up to 5 years

Secondary Outcomes (10)

• Incidence of Adverse Events Related to Treatment

  Up to 5 years

• Objective Response Rate (ORR) per iRECIST

  Up to 5 years

• CD8+ TIL and intra-tumoral myeloid cell density

  Up to 5 years

• Progression-free Survival (PFS)

  Up to 5 years

• Overall Survival (OS)

  Up to 5 years

Study Arms (1)

Healthy Donor Fecal Microbiota Transplant (hdFMT) with Pembrolizumab

EXPERIMENTAL

The hdFMT along with an intestinal biopsy will be performed as outpatient by a gastroenterologist. The hdFMT is infused into the colon by performing a colonoscopy (Treatment Phase 1) and by a sigmoidoscopy or oral capsules (Treatment Phase 2). FMT will be performed on Cycle 1 Day 1 and Cycle 3 Day 1 during Treatment Phase 1 and every 9 weeks starting with Cycle 4 Day 1 during Treatment Phase 2. Pembrolizumab, 200mg, will be administered as a 30-minute IV infusion every 3 weeks starting Cycle 1 Day 1 (same day as the hdFMT), and continue on Day 1 of each 21-day cycle.

Drug: Healthy Donor Fecal Microbiota Transplant (hdFMT); Drug: Pembrolizumab

Interventions

Healthy Donor Fecal Microbiota Transplant (hdFMT) DRUG

FMT is a procedure in which fecal matter or stool is collected from a tested donor, mixed with a saline or other solution, strained and infused into the colon by performing a colonoscopy and sigmoidoscopy, or, administered orally in the form of capsules. The FMT consists of introducing normal bacterial flora contained in the stool collected from a healthy donor into the small intestine. In this case, the hdFMT will be administered on Cycle 1 Day 1 and Cycle 3 Day 1 during Treatment Phase 1 and every 9 weeks starting with Cycle 4 Day 1 during Treatment Phase 2.

Healthy Donor Fecal Microbiota Transplant (hdFMT) with Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab, 200mg, will be administered as a 30-minute IV infusion every 3 weeks starting Cycle 1 Day 1 (same day as the FMT), and continue on Day 1 of each 21-day cycle.

Also known as: Keytruda

Healthy Donor Fecal Microbiota Transplant (hdFMT) with Pembrolizumab

Eligibility Criteria

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

You may qualify if:

• Male participants:
• A male participant must agree to use a contraception as detailed per protocol of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants:
• A female participant is eligible to participate if she is not pregnant per protocol, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP); OR
• A WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and for at least 120 days after the last dose of study treatment.
• Histologically or cytologically confirmed diagnosis of stage IV PD-L1+ NSCLC.
• NOTE: Patients with either squamous or non-squamous NSCLC may enroll.
• NOTE: Documented PD-L1 status (defined as 1% or greater) as determined by immunohistochemistry with anti-PD-L1 antibody (IHC 22C3 pharmDx or other FDA approved diagnostic method) from a core or excisional biopsy (fine needle aspirate is not sufficient).
• NOTE: Patients with small cell, large cell, neuroendocrine and/or sarcomatoid NSCLC are excluded.
• Participants must have progressed on treatment with an anti-PD(L)1 ICI administered either as monotherapy or in combination with other checkpoint inhibitors or other standard/investigational therapies. PD-1 treatment progression is defined by meeting all the following criteria:
• Has received at least 2 doses of an approved anti-PD(L)1 ICI administered as a single agent, in combination with chemotherapy, and/or in combination with other investigational therapy.
• Participants who progressed on/within 3 months of adjuvant therapy with anti-PD(L)1 ICI will eligible.
• Demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no sooner than 4 weeks from the date of the first documented PD.
• Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/anti-PD-L1 mAb.

You may not qualify if:

• Diagnosis of NSCLC histologies other than squamous and/or adenocarcinoma histologies including small cell, large cell, neuroendocrine and/or sarcomatoid histologies.
• Prior therapies:
• Receipt of prior agent(s) targeting the intestinal microbiome including but not limited to: FMT, defined bacterial consortia, single bacterial species and/or microbiota derived peptides.
• Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.
• Prior radiotherapy within 2 weeks of start of study intervention.
• Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
• A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to disease including CNS disease.
• Presence of an absolute contraindication(s) to FMT administration
• Toxic megacoon
• Severe dietary allergies (e.g. shellfish, nuts, seafood)
• Inflammatory bowel disease
• Patients who have not adequately recovered (i.e., ≤Grade 1 or at baseline or ≤Grade 2 endocrinopathy) from adverse events (AEs) due to a previously administered agent.
• A WOCBP who has a positive urine pregnancy test at Screening (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received a live vaccine within 30 days prior to the first dose of study drug.
• Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), SARS-CoV-2 and typhoid vaccine.

Sponsors & Collaborators

• Diwakar Davar: lead
• Gateway for Cancer Research: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Diwakar Davar, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Rose, RN, BSN

CONTACT

412-647-8587; kennaj@upmc.edu

Danielle L Bednarz, RN

CONTACT

412-623-1191; bednarzdl@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine - Hematology, Oncology

Study Record Dates

• First Submitted: December 20, 2022
• First Posted: January 3, 2023
• Study Start: January 8, 2025
• Primary Completion (Estimated): December 31, 2036
• Study Completion (Estimated): December 31, 2036
• Last Updated: March 23, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)