Using healthy donor microbiome to treat steroid-resistant skin and gut issues in cancer patients

Phase II Trial of Healthy-donor Derived Full-spectrum Microbiome Therapeutic MTP-101-C in Steroid Relapse/Refractory Immune-related Cutaneous Adverse Events (irCAEs) and Immune-mediated Colitis (IMC) (FMT-ELIMINATE)

This study is testing whether a treatment made from healthy gut bacteria can help cancer patients with skin and gut problems that don’t improve with steroids.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pittsburgh (Academic / other)
• Drugs / interventions: dupilumab, rituximab, infliximab, vedolizumab, chemotherapy, radiation, prednisone, tofactinib
• Locations: 1 site (Pittsburgh, Pennsylvania)
• Trial ID: NCT06499896 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of encapsulated fecal microbiota from healthy donors (MTP-101-C) to treat patients experiencing steroid-refractory immune-related cutaneous adverse events (irCAEs) and immune-mediated colitis (IMC) following anti-PD-1 or anti-CTLA-4 therapy. Over a 42-day period, participants will receive MTP-101-C while tapering off corticosteroids. The study aims to identify specific gut bacteria associated with these adverse events and assess the effectiveness of the microbiome treatment in alleviating symptoms. Patients will be monitored for changes in their condition through validated assessment scales and biomarker analysis.

Who should consider this trial

Good fit: Ideal candidates include cancer patients undergoing anti-PD-1 or anti-CTLA-4 therapy who are experiencing steroid-refractory skin or gut issues.

Not a fit: Patients who do not have clinically confirmed irCAEs or IMC, or those who are not receiving immunotherapy, may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from severe immune-related side effects of cancer immunotherapy.

How similar studies have performed: Previous studies have shown promising results using fecal microbiota transplants in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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.
* NOTE: Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days.

Cohort 2 (steroid-relapsed/refractory Grade ≥3 IMC) 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 (TNFα inhibitor infliximab OR α₄β₇ integrin inhibitor vedolizumab) prior to enrollment.
* Patients must have received steroids to be eligible.
* Steroid "resistant" disease: patients whose symptoms responded (reduction in a CTCAE grade) initially but who developed recurrence upon steroid taper or discontinuation.
* Steroid "refractory" disease: patients whose symptoms have not clinically improved by a CTCAE grade in ≥48 hours or maximum of 14 days.

  * Patient may have received any number of lines of prior systemic therapy.
  * Patient with any solid tumor or hematologic malignancy are eligible.
  * Patient must not be receiving concurrent radiation therapy.
  * Willingness to undergo cohort-specific evaluation.
* Cohort 1: Dermatologic evaluation, and skin biopsy evaluation prior to and after MTP-101-C administration.
* Cohort 2: GI evaluation, and endoscopic evaluation including colonoscopies prior to and after MTP-101-C administration.

  * Willingness to undergo correlative blood and stool sampling.
  * Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
* Patients with ECOG PS 2 wherein the decline in PS from baseline is deemed secondary to IMC may be enrolled at the discretion of Sponsor-Investigator.
* Patients with ECOG PS 2 wherein PS is at baseline and deemed secondary to disease are excluded.

  * Have adequate organ function per specimens must be collected within 7 days prior to the start of study treatment.

Exclusion Criteria:

* 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

Where this trial is running

Pittsburgh, Pennsylvania

• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Diwakar M Davar, MD, PhD — UPMC Hillman Cancer Center
• Study coordinator: Danielle L Bednarz, RN

Conditions Immune-mediated Colitis; Immune-related Dermatitis; gut microbiome; anti-PD-1 therapy