Study of Healthy Donor FMT (hdFMT) and Pembrolizumab in Relapsed/Refractory (R/R) PD-L1 Positive NSCLC

Required: PD-L1 (CD274) overexpression (1% or greater by IHC (22C3 pharmDx or other FDA approved method))

Documented PD-L1 status (defined as 1% or greater) as determined by immunohistochemistry with anti-PD-L1 antibody (IHC 22C3 pharmDx or other FDA approved diagnostic method)

Allowed: EGFR oncogenic driver mutation

Patients with known oncogenic driver (including but not limited to EGFR, ALK, ROS, MET alterations) must have received and progressed past driver-specific therapy

Allowed: ALK oncogenic driver alteration

Patients with known oncogenic driver (including but not limited to EGFR, ALK, ROS, MET alterations) must have received and progressed past driver-specific therapy

Allowed: ROS1 oncogenic driver alteration

Patients with known oncogenic driver (including but not limited to EGFR, ALK, ROS, MET alterations) must have received and progressed past driver-specific therapy

Allowed: MET oncogenic driver alteration

Patients with known oncogenic driver (including but not limited to EGFR, ALK, ROS, MET alterations) must have received and progressed past driver-specific therapy

Must have received: anti-PD-1 therapy

Participants must have progressed on treatment with an anti-PD(L)1 ICI administered either as monotherapy or in combination with other checkpoint inhibitors or other standard/investigational therapies. PD-1 treatment progression is defined by meeting all the following criteria: Has received at least 2 doses of an approved anti-PD(L)1 ICI administered as a single agent, in combination with chemotherapy, and/or in combination with other investigational therapy. Participants who progressed on/within 3 months of adjuvant therapy with anti-PD(L)1 ICI will eligible. Demonstrated disease progression after anti-PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no sooner than 4 weeks from the date of the first documented PD. Progressive disease has been documented within 12 weeks from the last dose of anti-PD-1/anti-PD-L1 mAb.

Cannot have received: agent targeting the intestinal microbiome (FMT, defined bacterial consortia, single bacterial species, microbiota derived peptides)

Receipt of prior agent(s) targeting the intestinal microbiome including but not limited to: FMT, defined bacterial consortia, single bacterial species and/or microbiota derived peptides.

Cannot have received: chemotherapy

Exception: within 2 weeks (or 4 half lives) prior to study Day 1

Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.

Cannot have received: targeted therapy

Exception: within 2 weeks (or 4 half lives) prior to study Day 1

Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.

Cannot have received: small molecule therapy

Exception: within 2 weeks (or 4 half lives) prior to study Day 1

Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.

Cannot have received: radiation therapy

Exception: within 2 weeks of start of study intervention; 2-week washout permitted for palliative radiation (≤2 weeks of radiotherapy) to disease including CNS disease

Prior radiotherapy within 2 weeks of start of study intervention.