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)
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.
• 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.