Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer
- Conditions
- MesotheliomaMesotheliomas PleuralMesothelioma PeritoneumCholangiocarcinomaNon Small Cell Lung CancerMesothelioma, MalignantMesothelioma; PleuraCholangiocarcinoma RecurrentOvarian CancerNon Small Cell Lung Cancer Metastatic
- Interventions
- Registration Number
- NCT03907852
- Lead Sponsor
- TCR2 Therapeutics
- Brief Summary
Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing a single-domain antibody that recognizes human Mesothelin, fused to the CD3-epsilon subunit which, upon expression, is incorporated into the endogenous T cell receptor (TCR) complex.
This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 36
- Patient is at least 18 years of age at the time the Informed Consent is signed.
- Patient has a pathologically confirmed diagnosis of either Malignant Pleural/Peritoneal Mesothelioma (MPM), Serous Ovarian Adenocarcinoma, Cholangiocarcinoma, or Non-Small Cell Lung Cancer (NSCLC) at screening.
- Patient's tumor has been pathologically reviewed by the central laboratory. For Serous Ovarian Adenocarcinoma, patients must have confirmed positive MSLN expression on >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by immunohistochemistry (IHC). Ovarian patients will subsequently be stratified into two groups: high MSLN expression (>/= 50% of tumor cells that are 2+ and/or 3+) or low MSLN expression (>/= 30% of tumor cells that are 1+, 2+, and/or 3+ not meeting criteria for the high MSLN expression group). MPM patients must have MSLN expression of >/= 50% of tumor cells that are 2+ and/or 3+ by IHC. Cholangiocarcinoma and NSCLC patients must have MSLN expression of >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by IHC.
- Prior to gavo-cel infusion, patients must have received at least 1 systemic standard of care therapy for metastatic or unresectable disease, with the exception of Cholangiocarcinoma patients who may have elected not to pursue standard frontline therapy. Regardless of tumor type, patients must not exceed 5 prior lines of therapy (excluding bridging therapy and surgical procedures). More details provided in the clinical protocol.
- Patient has an Eastern Cooperative Oncology Group performance status 0 or 1.
- Patient has a left ventricular ejection fraction > 45% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
- Patient is fit for leukapheresis and has adequate venous access for the cell collection.
- Patient must have adequate organ function as indicated by the laboratory values in the clinical protocol
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Lymphodepletion followed by gavo-cel gavo-cel fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab gavo-cel fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab gavo-cel fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel Lymphodepletion followed by gavo-cel fludarabine fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel Lymphodepletion followed by gavo-cel cyclophosphamide fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab Nivolumab fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab cyclophosphamide fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab fludarabine fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab fludarabine fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab cyclophosphamide fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab Nivolumab fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab Ipilimumab fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel
- Primary Outcome Measures
Name Time Method Phase 1- Primary Objective DLTs within 28 days post-treatment Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.
Phase 2- Primary Objective ORR at 3 months; DCR based on ORR + SD lasting at least 8 weeks To evaluate the efficacy of autologous genetically modified T cells (gavo-cel), with or without immuno-oncology agents, in patients with MSLN-expressing unresectable, metastatic, or recurrent cancers as determined by overall response rate and disease control rate using RECIST v1.1 (or mesothelioma-specific RECIST criteria, if applicable).
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (11)
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Duke University
🇺🇸Durham, North Carolina, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
National Cancer Institute
🇺🇸Bethesda, Maryland, United States
University of Miami Sylvester Cancer Center
🇺🇸Miami, Florida, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Columbia University Medical Center
🇺🇸New York, New York, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States