Status:

RECRUITING

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

Lead Sponsor:

Diwakar Davar

Collaborating Sponsors:

Stanley Marks Fund for Cancer Research

Cures Within Reach

Conditions:

Immune-mediated Colitis (IMC)

Immune-related Dermatitis

Eligibility:

All Genders

18+ years

Phase:

PHASE2

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 re...

Detailed Description

The study will be conducted over a 42-day period. Patients receiving anti-PD(L)1 and/or anti-CTLA-4 singly or in combination with other investigational agents are eligible to enroll. Enrollment is not...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

January 23 2025

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

September 30 2030

Estimated Enrollment :

30 Patients enrolled

Trial Details

Trial ID

NCT06499896

Start Date

January 23 2025

End Date

September 30 2030

Last Update

January 29 2025

Active Locations (1)

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UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232