Healthy-donor Microbiome MTP-101-C in Steroid Relapse/Refractory Immune-related Cutaneous Adverse Events (irCAEs) and Immune-mediated Colitis (IMC)

NCT06499896 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCC 23-158
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple retrospective studies suggest that the administration of corticosteroids to treat irAEs is safe, and does not compromise efficacy of ICI therapy in cancer patients. While \~67% of patients respond to corticosteroids, 33% of patients require biologic therapy such as TNFα inhibitors (e.g. infliximab), integrin α4β7 inhibitors (e.g. vedolizumab), or JAK/STAT inhibitors (e.g. tofactinib). This study aims to determine that distinct pathobionts govern the development of irCAE and IMC; and that the administration of hdFMT may reverse steroid-refractory irCAEs or IMC. The use of hdFMT has been shown to be effective in steroid and biologic (TNFα and/or integrin α₄β₇ inhibitor) refractory colitis in PD-1 and/or CTLA-4 ICI treated cancer patients in single-institution case series.

Conditions

Immune-mediated Colitis (IMC); Immune-related Dermatitis

Keywords

gut microbiome; anti-PD-1 therapy

Outcome Measures

Primary Outcomes (2)

• Incidence of adverse events (AEs)

  Incidence of adverse events (AEs) in ICB-treated cancer patients treated with MTP-101-C.

  Up to 2 months

• Incidence of Dose-Limiting Toxicities (DLTs)

  Incidence of dose-limiting toxicities (DLTs) in ICB-treated cancer patients treated with MTP-101-C. DLT is defined as any adverse event(s) (AEs) considered possibly, probably, or definitely related to MTP-101-C, which occur during the treatment phase. During DLT monitoring period, no further accrual will be permitted. Any patient who has started the studied treatment will be evaluable for safety. AEs will be considered DLTs if deemed related to study therapy: Hematologic: Grade 4 neutropenia, Febrile neutropenia, Grade ≥ 3 neutropenic infection, Grade ≥ 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia. Non-hematologic: Grade ≥ 3 toxicities (non-laboratory), Grade ≥ 3 nausea, vomiting or diarrhea despite maximal medical intervention, Grade 4 aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Other (non-AST/ALT) non-hematologic Grade ≥ 3 laboratory value if the abnormality leads to overnight hospitalization

  Up to 2 months

Secondary Outcomes (6)

• Resolution of steroid relapsed/refractory irCAEs (cohort 1)

  Up to 2 months

• Resolution of steroid relapsed/refractory IMC (cohort 2)

  Up to 2 months

• Resolution of IMC following MTP-101-C in steroid relapsed/refractory irCAE (cohort 1)

  Up to 2 months

• Resolution of IMC following MTP-101-C in steroid relapsed/refractory IMC (cohort 2)

  Up to 2 months

• Patient Reported Outcomes - FACT-ICM

  At Screening, Day +28 through Day +35, Day +42 through Day +49

Study Arms (2)

MTP-101-C (Cohort 1: Steroid R/R biologic-naive dermatitis)

EXPERIMENTAL

Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors). Dosing: 5 capsules/day (Day 1); 2 capsules/day (D2-D28)

Biological: MTP-101-C

MTP-101-C (Cohort 2: Steroid R/R biologic-naive colitis)

EXPERIMENTAL

Patients given MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors). Dosing: 5 capsules/day (Day 1); 2 capsules/day (D2-D28)

Biological: MTP-101-C

Interventions

MTP-101-C BIOLOGICAL

MTP-101-C is a screened, freeze-dried, encapsulated, full spectrum, healthy donor fecal microbiota product.

MTP-101-C (Cohort 1: Steroid R/R biologic-naive dermatitis); MTP-101-C (Cohort 2: Steroid R/R biologic-naive colitis)

Eligibility Criteria

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

You may qualify if:

• Able to swallow oral medication.
• The participant provides written informed consent for the trial.
• Willingness to use contraception for duration of trial participation. Male participants: A male participant must agree to use a contraception per 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, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) per protocol; OR A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of study treatment.
• Clinically confirmed inflammatory irCAE or endoscopically confirmed IMC. Cohort 1 (irCAE): Patients with maculopapular rash, psoriasiform, lichenoid eruptions or bullous pemphigoid of at least grade 3 severity per CTCAE grading system (i.e. \>30% BSA with moderate or severe symptoms) during Screening.
• Cohort 2 (IMC): Endoscopically confirmed inflammatory colitis as determined by colonoscopy or flexible sigmoidoscopy during Screening with minimum severity per Mayo endoscopic subscore 1-¬3 \[MES1-3\].
• Prior receipt of anti-PD(L)1 and/or anti-CTLA-4 singly or in combination with other approved or investigational agents including chemotherapy or targeted therapy.
• NOTE: Patient may have received or are receiving ICI therapy as standard-of-care or part of a clinical trial.
• Patient must have received treatment with an anti-PD-(L)1 ICI, anti-CTLA-4 ICI singly and/or in combination with other approved and/or investigational anti-cancer agent(s), as their most recent therapy prior to development of colitis.
• Cohort 1 (steroid relapsed/refractory Grade ≥3 irCAE) only
• Receipt of high-dose systemic corticosteroids defined as 1-2mg/kg prednisone equivalent daily (either oral or intravenous) with a taper over 4-6 weeks as defined by society consensus guidelines102-105; AND
• No receipt of biologic such as but not limited to (dupilumab, rituximab) prior to enrollment.
• NOTE: Patients must have received steroids to be eligible.
• NOTE: Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation.

You may not qualify if:

• Multiple irAEs besides irCAE or IMC.
• Patients with concurrent ≥Grade 3 irAEs besides irCAE or IMC that necessitate systemic immune suppression are not candidates for this trial.
• Patients with irCAE and/or IMC that are not otherwise clarified in Section 5.1.5 (irCAE including alopecia etc.) are not candidates for this trial.
• Patients with concomitant irAEs that are well controlled (≤Grade 1 or Grade 2 on repletion medication) may be enrolled at the discretion of Sponsor-Investigator.
• Diagnosis of immunodeficiency, immunosuppression or any other form of immunosuppressive therapy besides steroids/biologics within 7 days prior to the first dose of MTP-101-C treatment.
• Patients at high risk of MDRO colonization including: nursing home residence, age \>85, underlying diseases (dementia, poorly controlled diabetes, chronic wounds), in-dwelling medical devices (urinary catheters, feeding tubes, PEG tubes) and a prior history of MDRO colonization.
• Contraindication to endoscopy (cohort 2 only).
• Contraindication to MTP-101-C administration.
• Any prior head/neck and/or abdominal surgery resulting in potentially altered absorption of orally administered FMT pills.
• Active bacterial infection requiring systemic antibiotic therapy.
• Received live vaccines within 30 days prior to the first dose of study treatment and while participating in the study

Sponsors & Collaborators

• Cures Within Reach: collaborator
• Diwakar Davar: lead
• Stanley Marks Fund for Cancer Research: collaborator

Study Sites (1)

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Study Officials

• Diwakar M Davar, MD, PhD

  UPMC Hillman Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle L Bednarz, RN

CONTACT

4126231191; bednarzdl@upmc.edu

Amy Rose, RN

CONTACT

4126478587; kennaj@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medical oncology

Study Record Dates

• First Submitted: July 1, 2024
• First Posted: July 15, 2024
• Study Start: January 23, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2031
• Last Updated: February 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)