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 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 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.

4. asymptomatic or minimally symptomatic active metastases, with controlledsteriod use and no imminent CNS complications.

• Participants with leptomeningeal disease.

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

• Participants who are solid organ transplantation recipients or likely to receivesolid 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 toenrollment.

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