LND101 for Fecal Microbiota Transplantation in Combination With Immune Checkpoint Blockade in Advanced Melanoma

Inclusion criteria

• Participants must have a confirmed histological diagnosis of cutaneous melanoma or melanoma of unknown primary.
• Participants must have stage IV or advanced unresectable disease.
• No prior ICB treatment for advanced unresectable or metastatic disease. Participants may have received adjuvant or neoadjuvant ICB if last dose was given ≥ 6 months prior to enrollment
• Prior targeted therapy with BRAF/MEK inhibition in the adjuvant or advanced / metastatic setting is permitted if at least 2 weeks have elapsed between the last dose and study enrollment. Participants must have recovered to ≤ grade 1 from all toxicity related to BRAF/MEK inhibition
• Prior radiation therapy is permitted if at least 7 days have elapsed between the last fraction and study enrollment. Participants must have recovered to ≤ grade 1 from all toxicity related to prior radiotherapy.
• Previous major surgery is permitted provided that surgery occurred ≥ 14 days prior to participant enrollment and that wound healing has occurred.
• Participants must have measurable disease as per RECIST 1.1/ iRECIST.
• Participants must be at least 18 years of age.
• Participants must have an ECOG performance status of 0, 1, or 2.
• The participant's standard-of-care ICB regimen must be selected prior to enrollment and must stay the same, regardless of arm assignment, post-enrollment
• Participants must demonstrate adequate organ function Participants must be able to ingest capsules.
• Participants must consent to provision of samples of blood and stool for correlative marker analysis.
• Participants must consent to provision of, and investigator must agree to submit, a representative archival formalin fixed paraffin block of tumour tissue for correlative analyses when tumour tissue is available.
• Participants must have access to provincially-funded standard-of-care ICB treatment.
• Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Participants must be accessible for treatment and follow-up. Investigators must assure themselves the participants randomized on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.
• Protocol ICB treatment must begin within 14 calendar days after participant enrollment.
• Participants of childbearing potential must have agreed to use a highly effective contraceptive method.

Exclusion criteria

• Participants with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.
• Participants who have received antibiotics within 14 days of enrollment.
• Participants with systemic prednisone use \> 10mg per day or equivalent dose.
• Participants with concurrent treatment with other anti-cancer therapy.
• Participants that have received live attenuated vaccination administered within 30 days prior to randomization. Note: Seasonal vaccines for influenza and COVID-19 are generally inactivated vaccines and are allowed. Intranasal vaccines are live vaccines and not allowed.
• For participants with history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
• Participants with absolute contraindications to FMT including: a) Toxic megacolon; b) Inflammatory bowel disease; c) Severe dietary allergies
• Participants with hypersensitivity to PegLyte®
• Participants with symptomatic brain metastases unless brain lesions are shown to be stable, according to the following definitions:
• without evidence of progression for at least four weeks prior to randomization and have no evidence of new or enlarging brain metastases; or
• treated with surgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases; or
• treated with stereotactic radiosurgery and without evidence of progression prior to randomization and have no evidence of new or enlarging brain metastases.
• asymptomatic or minimally symptomatic active metastases, with controlled steriod use and no imminent CNS complications.
• Participants with leptomeningeal disease.
• Participants with any uncontrolled autoimmune disease that requires active immunosuppressive agents.
• Participants who are solid organ transplantation recipients or likely to receive solid organ transplants in the future.
• Participants living with HIV.
• Participants with active infection. Participants may be eligible following recovery. Participants requiring antibiotics require 2-week washout period prior to enrollment.
• Participants that are pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial.