Healthy-donor Microbiome MTP-101-C in Steroid Relapse/Refractory Immune-related Cutaneous Adverse Events (irCAEs) and Immune-mediated Colitis (IMC)
NCT Number: NCT06499896
Acronym: FMT-ELIMINATE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Immune-mediated Colitis (IMC)|Immune-related Dermatitis
Interventions: BIOLOGICAL: MTP-101-C
Sponsor: Diwakar Davar
Collaborators: Stanley Marks Fund for Cancer Research|Cures Within Reach
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 30
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2030-08
Locations: UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, 15232, United States

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.

Primary Outcome Measures: 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 Outcome Measures: Resolution of steroid relapsed/refractory irCAEs (cohort 1), Resolution of steroid relapsed/refractory irCAEs (cohort 1) following MTP-101-C using cohort -specific endpoints including modified CTCAE grading system (cohort 1), Up to 2 months|Resolution of steroid relapsed/refractory IMC (cohort 2), Resolution of steroid relapsed/refractory IMC (cohort 2) following MTP-101-C using cohort -specific endpoints including modified CTCAE grading system (cohort 1) or endoscopic assessment scale Full Mayo Score (FMS) (cohort 2). FMS includes Partial Mayo Score (PMS) plus endoscopic findings. PMS assesses Stool frequency (per day - normal number of stools to ≥ 5 more, Rectal bleeding (none to blood alone passes) and Physician's global assessment (normal to severe disease), all with scores ranging from 0 to 3. Scores range from 0 - 9 points. Endoscopic score findings range from 0 - 3. Total full scores range from 0 to12, with higher scores indicating more severe ulcerative colitis., Up to 2 months|Resolution of IMC following MTP-101-C in steroid relapsed/refractory irCAE (cohort 1), Resolution of IMC following MTP-101-C in steroid relapsed/refractory irCAE (cohort 1) or IMC (cohort 2) using clinical endpoint Partial Mayo Score (PMS), which assesses Stool frequency (per day - normal number of stools to ≥ 5 more, Rectal bleeding (none to blood alone passes) and Physician's global assessment (normal to severe disease), all with scores ranging from 0 to 3. Scores range from 0 - 9 points, with higher scores indicating more severe ulcerative colitis., Up to 2 months|Resolution of IMC following MTP-101-C in steroid relapsed/refractory IMC (cohort 2), Resolution of IMC following MTP-101-C in steroid relapsed/refractory irCAE (cohort 1) or IMC (cohort 2) using clinical endpoint Partial Mayo Score (PMS), which assesses Stool frequency (per day - normal number of stools to ≥ 5 more, Rectal bleeding (none to blood alone passes) and Physician's global assessment (normal to severe disease), all with scores ranging from 0 to 3. Scores range from 0 - 9 points, with higher scores indicating more severe ulcerative colitis., Up to 2 months|Patient Reported Outcomes - FACT-ICM, The FACT-ICM is a self-administered questionnaire that measures quality of life within the prior 7 days in patients being treated with immunotherapy, using 52 items with a 5-point Likert-type scale, (0 = Not at all to 5 = Very Much). Subscales include Physical Well-Being max score=28), Social/Family Well-Being (max score=28), Emotional Well-Being (max score=24), Functional Well-Being (max score=28), Immune Checkpoint Modulator Subscale (max score=100). Total scores= 0 to 208, with higher scores indicating better quality of life., At Screening, Day +28 through Day +35, Day +42 through Day +49|Patient Reported Outcomes - FACIT-general, FACIT-general is a self-administered questionnaire that measures quality of life within the prior 7 days in patients being treated with immunotherapy, using 27 items with a 5-point Likert-type scale, (0 = Not at all to 5 = Very Much). Subscales include Physical Well-Being max score=28), Social/Family Well-Being (max score=28), Emotional Well-Being (max score=24), Functional Well-Being (max score=28), Total scores= 0 to 108, with higher scores indicating better quality of life., At Screening, Week 1, Week 2, Week 3, Week 4