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 ormelanoma of unknown primary.

• Participants must have stage IV or advanced unresectable disease.

• No prior ICB treatment for advanced unresectable or metastatic disease. Participantsmay have received adjuvant or neoadjuvant ICB if last dose was given ≥ 6 monthsprior 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 lastdose and study enrollment. Participants must have recovered to ≤ grade 1 from alltoxicity related to BRAF/MEK inhibition

• Prior radiation therapy is permitted if at least 7 days have elapsed between thelast fraction and study enrollment. Participants must have recovered to ≤ grade 1from all toxicity related to prior radiotherapy.

• Previous major surgery is permitted provided that surgery occurred ≥ 14 days priorto 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 enrollmentand must stay the same, regardless of arm assignment, post-enrollment

• Participants must demonstrate adequate organ function Participants must be able toingest capsules.

• Participants must consent to provision of samples of blood and stool for correlativemarker analysis.

• Participants must consent to provision of, and investigator must agree to submit, arepresentative archival formalin fixed paraffin block of tumour tissue forcorrelative 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 applicablelocal and regulatory requirements. Each participant must sign a consent form priorto enrollment in the trial to document their willingness to participate.

• Participants must be accessible for treatment and follow-up. Investigators mustassure themselves the participants randomized on this trial will be available forcomplete documentation of the treatment, adverse events, and follow-up.

• Protocol ICB treatment must begin within 14 calendar days after participantenrollment.

• Participants of childbearing potential must have agreed to use a highly effectivecontraceptive method.

Exclusion Criteria:

• Participants with a prior or concurrent malignancy whose natural history ortreatment has the potential to interfere with the safety or efficacy assessment ofthe investigational regimen.

• Participants who have received antibiotics within 14 days of enrollment.

• Participants with systemic corticosteroid use > 10mg per day.

• Participants with concurrent treatment with other anti-cancer therapy.

• Participants that have received live attenuated vaccination administered within 30days prior to randomization. Note: Seasonal vaccines for influenza and COVID-19 aregenerally inactivated vaccines and are allowed. Intranasal vaccines are livevaccines and not allowed.

• For participants with history of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated. Participantswith a history of hepatitis C virus (HCV) infection must have been treated andcured. For participants with HCV infection who are currently on treatment, they areeligible 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 bestable, according to the following definitions:

1. without evidence of progression for at least four weeks prior to randomizationand have no evidence of new or enlarging brain metastases; or

2. treated with surgery and without evidence of progression prior to randomizationand have no evidence of new or enlarging brain metastases; or

3. treated with stereotactic radiosurgery and without evidence of progressionprior to randomization and have no evidence of new or enlarging brainmetastases.

• Participants with leptomeningeal disease.

• Participants with any uncontrolled autoimmune disease that requires activeimmunosuppressive agents.

• Participants who are solid organ transplantation recipients.

• Participants living with HIV.

• Participants with active infection. Participants may be eligible following recovery.Participants requiring antibiotics require 2-week washout period prior toenrollment.

• Participants that are pregnant, breastfeeding, or expecting to conceive or fatherchildren within the projected duration of the trial.