Immune Checkpoint Blockade and Chemotherapy With or Without Fecal Microbiota Transplant in Advanced Non-Small Cell Lung Cancer

Prior treatment

• 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 with concurrent treatment with other anti-cancer therapy, including experimental therapies.
• Participants that have received live attenuated vaccination administered within 28 days prior to randomization.
• Participants with symptomatic central nervous system (CNS) metastases and/or CNS metastases requiring immunosuppressive doses of systemic corticosteroids (\>10 mg/day prednisone equivalents). Participants with known central nervous system metastases who are asymptomatic and on a stable dose of corticosteroids ≤ 10 mg/day prednisone equivalents are eligible.
• Participants who are solid organ transplantation recipients or likely to receive solid organ transplants in the future
• Participants with active infection may be eligible following recovery. Participants who have received antibiotics require a 14-day wash-out prior to enrollment. Participants should not receive prebiotics or probiotics while receiving protocol treatment and require at least a 3-day wash-out prior to enrollment.
• HIV-infected participants on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. For participants with evidence 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 the following concomitant illnesses: impaired cardiovascular function (uncontrolled congestive heart failure requiring treatment (NYHA grade \> 2), uncontrolled hypertension, acute myocardial cardiac ischemia or unstable angina \<6 months prior to study entry, and severe cardiac arrhythmia).

Other illness

• Large-cell neuroendocrine carcinoma (LCNEC), pulmonary carcinoid tumour or mixed small cell and non-small cell lung cancer are not eligible. Participants with adenosquamous carcinoma, large-cell carcinoma without a neuroendocrine component, and sarcomatoid carcinomas are eligible
• Participants with absolute contraindications to FMT including: toxic megacolon; inflammatory bowel disease; severe dietary allergies (e.g. shellfish, nuts, seafood) and; total colon resection.
• Participants with hypersensitivity to PegLyte® or generic equivalents.
• Participants with leptomeningeal disease.
• Participants with any uncontrolled autoimmune disease that requires active immunosuppressive agents. Participants with vitiligo, type I diabetes, resolved childhood asthma/atopy are eligible.

Other

• Participants with systemic prednisone use \>10mg per day or equivalent dose (unless intranasal or inhaled).
• Participants that are pregnant, breastfeeding or expecting to conceive or father children within the projected duration of the trial.

• Participants must have histologically and/or cytologically confirmed advanced or metastatic squamous or non-squamous non-small cell lung cancer (NSCLC) that has negative or low (0-49%) PD-L1 TPS, without a driver mutation with an actionable first-line targeted therapy, for whom immune checkpoint blockade (ICB) + chemotherapy combination is indicated.
• Prior chemotherapy or immunotherapy for non-metastatic disease (e.g. adjuvant and/or neoadjuvant therapy) is allowed if at least 6 months have elapsed prior to enrollment.
• Previous major surgery is permitted provided that surgery occurred at least 14 days prior to participant enrollment and that wound healing has occurred.
• Local therapy, e.g. palliative extra-cranial radiation, is allowed provided a minimum of 14 days have elapsed between the last dose of radiation and date of enrollment.
• Local therapy, e.g. palliative extra-cranial radiation, is allowed provided a minimum of 14 days have elapsed between the last dose of radiation and date of enrollment.
• Participants must have measurable disease as per RECIST 1.1 criteria.
• Participants must be at least 18 years of age.
• ECOG performance status 0, 1 or 2.
• Participants must have adequate organ and marrow function measured within 28 days prior to enrollment.
• Participant must be able to ingest capsules.
• 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 consent to provision of samples of blood and stool for correlative marker analysis.
• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French.
• Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Participants must be accessible for treatment and follow-up.
• Protocol ICB + chemotherapy is to begin within 14 calendar days after participant enrollment. For the experimental arm, fecal microbiota transplant (FMT) is to begin within 7 calendar days of participant enrollment.
• Participants of childbearing potential must have agreed to use a highly effective contraceptive method.