This study is to determine if Healthy Donor FMT (hdFMT) improves the body's ability to fight cancer in patients with relapsed/refractory PD-L1 Positive NSCLC.
Not a woman of childbearing potential (WOCBP); OR
A WOCBP who agrees to follow the contraceptive guidance per protocol during the treatment period and for at least 120 days after the last dose of study treatment.
Histologically or cytologically confirmed diagnosis of stage IV PD-L1+ NSCLC.
NOTE: Patients with either squamous or non-squamous NSCLC may enroll.
Diagnosis of NSCLC histologies other than squamous and/or adenocarcinoma histologies including small cell, large cell, neuroendocrine and/or sarcomatoid histologies.
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.
Prior chemotherapy, targeted therapy, and/or small molecule therapy within 2 weeks (or 4 half lives) prior to study Day 1.
Prior radiotherapy within 2 weeks of start of study intervention.
Single group
Healthy Donor Fecal Microbiota Transplant (hdFMT)
DrugFMT is a procedure in which fecal matter or stool is collected from a tested donor, mixed with a saline or other solution, strained and infused into the colon by performing a colonoscopy and sigmoidoscopy, or, administered orally in the form of capsules. The FMT consists of introducing normal bacterial flora contained in the stool collected from a healthy donor into the small intestine. In this case, the hdFMT will be administered on Cycle 1 Day 1 and Cycle 3 Day 1 during Treatment Phase 1 and every 9 weeks starting with Cycle 4 Day 1 during Treatment Phase 2.
Pembrolizumab
DrugPembrolizumab, 200mg, will be administered as a 30-minute IV infusion every 3 weeks starting Cycle 1 Day 1 (same day as the FMT), and continue on Day 1 of each 21-day cycle.
Objective Response Rate (ORR) per RECIST v1.1
The proportion of patients with objective response (Complete Response (CR) or Partial Response (PR)) to R-FMT and pembrolizumab treatment in PD-1 primary refractory NSCLC as assessed per RECIST v1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. For non-target lesions: Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10mm short axis); PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Incidence of Adverse Events Related to Treatment
Frequency of Adverse Events and specifically ≥grade 2 irAEs per CTCAE v5.0 in PD-1 primary refractory NSCLC in patients treated with Healthy Donor FMT (hdFMT) and pembrolizumab, to assess overall safety, feasibility and tolerability of treatment.
Objective Response Rate (ORR) per iRECIST
The proportion of patients Complete Response (irCR) or Partial Response (irPR) to treatment as assessed per iRECIST. irCR:Disappearance of non-nodal lesions.All pathologic lymph nodes \<10 mm (short axis) (2 consecutive measurements ≥4 weeks apart); irPR :≥30% decrease from baseline (2 consecutive measurements ≥4 weeks apart). Disappearance of all non-nodal lesions.All pathologic lymph nodes \<10 mm (Non-Target Lesions:Any other than disappearance of all non-nodal lesions and reduction of pathologic lymph nodes \<10 mm). Baseline tumor burden: sum of single diameters (short axis for nodal lesions, longest diameter for other lesions) for target lesions. In subsequent scans, the diameters of new measurable lesions are added to the tumor burden. Re-treatment: ≤5 target lesions (=/≠ original lesions) are selected and a new baseline tumor burden will be established. (no distinct iRECIST assessment until radiographic progression per RECIST 1.1 is observed).
CD8+ TIL and intra-tumoral myeloid cell density
Percentage of CD8+ T cells in intra-tumoral myeloid cells in pre-treatment biopsy samples assess using multiplex IHC.
Progression-free Survival (PFS)
The median length of time from initiation of study drug(s) disease progression as defined by RECIST v1.1, or death. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The sum must also demonstrate an absolute increase of ≥5 mm. The appearance ≥1 new lesion(s) is considered progression.
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Diwakar Davar
Lead sponsor
University of Pittsburgh
Sponsor institution
Gateway for Cancer Research
Collaborator
