Phase II Feasibility Study of Healthy Donor FMT (hdFMT) and Pembrolizumab in Relapsed/Refractory (R/R) PD-L1 Positive NSCLC
概览
- 阶段
- 2 期
- 干预措施
- Healthy Donor Fecal Microbiota Transplant (hdFMT)
- 疾病 / 适应症
- Non Small Cell Lung Cancer
- 发起方
- Diwakar Davar
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- Objective Response Rate (ORR) per RECIST v1.1
- 状态
- 招募中
- 最后更新
- 上个月
概览
简要总结
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.
详细描述
The study evaluating the addition of Healthy Donor FMT (hdFMT) to pembrolizumab in PD-1 R/R NSCLC will be conducted over a 104-week period. Patients with anti-PD-1 R/R NSCLC are eligible to enroll. Prior exposure to microbiome modulating therapy is exclusionary. Suitable patients will be identified at the time of progression upon PD-1 monotherapy or PD-1 containing regimens. Patients will undergo a 35-day screening evaluation consisting of systemic staging scans, tumor biopsy, stool/blood serologic studies to confirm suitability. Once enrolled, patients will be seromatched with a suitable donor. Suitable donors are advanced cancer patients who have undergone PD-1 monotherapy and are currently in durable remission (median PFS \>24 months from initiation of PD-1 therapy) with no ongoing irAE as delineated below. Patients will receive Healthy Donor FMT (hdFMT) (induction) via colonoscopy on C1D1 and C3D1. R-FMT (maintenance) via sigmoidoscopy on C4D1 and will be repeated every 9 weeks. All patients will additionally receive pembrolizumab at 200mg every three weeks. Patients will be treated until disease progression or intolerable toxicity or completion of 2 years of therapy, whichever comes first.
研究者
Diwakar Davar
Assistant Professor of Medicine - Hematology, Oncology
University of Pittsburgh
入排标准
入选标准
- •Male participants:
- •A male participant must agree to use a contraception as detailed per protocol of this protocol during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
- •Female participants:
- •A female participant is eligible to participate if she is not pregnant per protocol, not breastfeeding, and at least one of the following conditions applies:
- •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.
- •NOTE: 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) from a core or excisional biopsy (fine needle aspirate is not sufficient).
- •NOTE: Patients with small cell, large cell, neuroendocrine and/or sarcomatoid NSCLC are excluded.
排除标准
- •Diagnosis of NSCLC histologies other than squamous and/or adenocarcinoma histologies including small cell, large cell, neuroendocrine and/or sarcomatoid histologies.
- •Prior therapies:
- •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
- •Prior radiotherapy within 2 weeks of start of study intervention.
- •Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- •A 2-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to disease including CNS disease.
- •Presence of an absolute contraindication(s) to FMT administration
- •Toxic megacoon
- •Severe dietary allergies (e.g. shellfish, nuts, seafood)
研究组 & 干预措施
Healthy Donor Fecal Microbiota Transplant (hdFMT) with Pembrolizumab
The hdFMT along with an intestinal biopsy will be performed as outpatient by a gastroenterologist. The hdFMT is infused into the colon by performing a colonoscopy (Treatment Phase 1) and by a sigmoidoscopy or oral capsules (Treatment Phase 2). FMT will be performed 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, 200mg, will be administered as a 30-minute IV infusion every 3 weeks starting Cycle 1 Day 1 (same day as the hdFMT), and continue on Day 1 of each 21-day cycle.
干预措施: Healthy Donor Fecal Microbiota Transplant (hdFMT)
Healthy Donor Fecal Microbiota Transplant (hdFMT) with Pembrolizumab
The hdFMT along with an intestinal biopsy will be performed as outpatient by a gastroenterologist. The hdFMT is infused into the colon by performing a colonoscopy (Treatment Phase 1) and by a sigmoidoscopy or oral capsules (Treatment Phase 2). FMT will be performed 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, 200mg, will be administered as a 30-minute IV infusion every 3 weeks starting Cycle 1 Day 1 (same day as the hdFMT), and continue on Day 1 of each 21-day cycle.
干预措施: Pembrolizumab
结局指标
主要结局
Objective Response Rate (ORR) per RECIST v1.1
时间窗: Up to 5 years
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.
次要结局
- Incidence of Adverse Events Related to Treatment(Up to 5 years)
- Objective Response Rate (ORR) per iRECIST(Up to 5 years)
- CD8+ TIL and intra-tumoral myeloid cell density(Up to 5 years)
- Progression-free Survival (PFS)(Up to 5 years)
- Overall Survival (OS)(Up to 5 years)
- 6-month Progression-free Survival(Up to 6 months)
- 1-year Progression-free Survival (PFS)(Up to 1 year)
- 2-year Progression-free Survival (PFS)(Up to 2 years)
- 1-year Overall Survival (OS)(Up to 1 year)
- 2-year Overall Survival (OS)(Up to 2 years)