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.
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.
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
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.
Parallel
MTP-101-C
Biological/VaccineMTP-101-C is a screened, freeze-dried, encapsulated, full spectrum, healthy donor fecal microbiota product.
Incidence of adverse events (AEs)
Incidence of adverse events (AEs) in ICB-treated cancer patients treated with MTP-101-C.
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
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)
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.
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.
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.
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Diwakar Davar
Lead sponsor
University of Pittsburgh
Sponsor institution
Stanley Marks Fund for Cancer Research
Collaborator
Cures Within Reach
Collaborator
