RMT in Combination With Durvalumab + Chemo in Untreated Adenocarcinoma NSCLC. A Randomized Double Blind Phase II Trial

Not pregnant or breast feeding. Evidence of post-menopausal status, or negative urine or serum pregnancy test for female pre-menopausal patients. Women will be considered postmenopausal if they have amenorrhea for 12 months without an alternative medical explanation

Dysphagia or inability to swallow medications

Squamous cell, large cell, or NSCLC NOS (not otherwise specified) histology or mixed tumors

Has untreated brain metastasis or active leptomeningeal carcinomatosis

Has a known sensitivity to any component of therapeutic agents used in this study

Receipt of any immunotherapy or investigational drug within 4 weeks prior to the first dose of study drug; and in the case of monoclonal antibodies 6 weeks prior to the first dose of study drug

Prior treatment with any other anti-PD-1, or PD-L1, including durvalumab or an anti-PD-L2 agent or an antibody or a small molecule targeting other immuno-regulatory receptors except as adjuvant therapy for NSCLC so long as it has been greater than six months since the last treatment

Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid

Recent major surgery within 4 weeks prior to entry into the study (excluding the placement of vascular access) that would prevent administration of study drug

Active or prior documented autoimmune disease within the past 2 years requiring systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.

Active documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis) who require immunosuppression or patients who exceed 10 mg/day of prednisone, or an equivalent corticosteroid are excluded

History of primary immunodeficiency

History of organ transplant that requires therapeutic immunosuppression

Taking daily probiotics (patients with last probiotic \> 4weeks prior to first dose of RMT are eligible)

History of Human Immunodeficiency Virus (HIV) (known HIV 1/2 antibodies positive) who are on anti-retroviral treatment for \< 6 months and absolute CD4 count\<500 (patients with HIV not meeting these criteria are eligible)

Has known active Hepatitis B or C. Active Hepatitis B is defined as a known positive HBsAg, and positive hepatitis B virus quantification assay (patients with history of Hepatitis B who have seroconversion i.e. Hepatitis B core antibody positive and Hepatitis B surface antibody positive are eligible). Active Hepatitis C is defined by a known positive Hep C Ab result and positive quantitative HCV RNA results (Patients with Hepatitis C who are on anti-viral suppressive therapy and negative quantitative HCV RNA results are eligible)

Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses

Myocardial infarction or stroke within 3 months prior to enrollment

History of systolic or diastolic heart failure with New York Heart Association (NYHA) class III or IV symptoms (refer to Appendix II)

Has active or prior history of (non-infectious) pneumonitis that required steroids or patients with interstitial lung disease

Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent

Known history of active tuberculosis. Patients with prior history of latent TB could be included if they have been treated previously with isoniazid.

Patients who are on chronic systemic antibiotic therapy (antibiotics for ≥60 consecutive days within 12 weeks of enrollment). Patients who receive systemic antibiotics between enrollment and start of RMT are eligible

Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving RMT

History of another primary malignancy (excluding non-melanoma skin cancer) within 5 years prior to starting RMT, except if the patient has undergone potentially curative therapy with no evidence of disease recurrence for 5 years since initiation of that therapy

Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results

What this study is about