NCT06499896

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

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)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Diwakar Davar · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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 limited by setting (adjuvant, metastatic) and/or line of therapy (1L, 2L etc.). Once enrolled, patients will be enrolled to receive MTP-101-C (encapsulated fecal microbiota, containing \~5 x 1011 bacteria derived from healthy donors) without prior antibiotic conditioning. MTP-101-C will be continued for 28 days during which steroids will be tapered rapidly. irAE endpoint assessment will be repeated following completion of hdFMT (D+28 to D+35) and at 6 weeks (D+42 to D+49). Biospecimens will be obtained periodically. The total duration of MTP-101-C therapy is 4 weeks. This study aims to determine distinct pathobionts govern the development of distinct irAEs including steroid-refractory irCAE or IMC; and that the administration of hdFMT ameliorates irCAE or IMC based on validated cohort-specific assessments: modified CTCAE grading system (cohort 1) or endoscopic assessment scale (full Mayo score, FMS) (cohort 2). Further, this trial aims to show that amelioration of inflammatory pathology is associated with key secondary objectives including: 1) improvements in an irAE toxicity-specific PRO FACT-ICM; and 2) clinically assessment scales. Also, this study will measure the correlation between symptom amelioration and changes in integrated biomarkers include measures of intestinal inflammation (fecal calprotectin), bacterial engraftment (metagenomic) and reactivity to donor bacteria (IgG-seq); exploring the effects of microbiome modulation upon time to steroid discontinuation, time to resumption of therapy, time to next treatment clinical remission by FMS, clinical remission by PMS, and key survival endpoints.

Conditions

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

Interventions

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

Timeline

• Start date: 2025-01-23
• Primary completion: 2027-09-30
• Completion: 2031-09-30
• First posted: 2024-07-15
• Last updated: 2026-02-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study