Multi-center, open-label, first in human Phase 1 study of the safety, tolerability, feasibility, and preliminary efficacy of the administration of genetically modified autologous T cells (CART-TnMUC1 cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen, TnMUC1 and activating the T cell (CART- TnMUC1 cells).
The Dose Escalation phase of the study is designed to identify the dose and regimen of CART-TnMUC1 cells that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with (1) advanced TnMUC1+ solid tumors (triple negative breast cancer, epithelial ovarian cancer, pancreatic cancer, and non-small cell lung cancer) and (2) advanced TnMUC1+ multiple myeloma in a parallel two-arm dose escalation study. The Dose Escalation phase is anticipated to enroll approximately 40 patients. The Expansion phase of the study is designed to assess the preliminary efficacy of CART-TnMUC1 cells administered intravenously to patients with TnMUC1+ solid tumors. The Expansion phase is anticipated to enroll approximately 72 patients (18 patients per each tumor indication).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
16
Single intravenous administration of genetically modified autologous T cells engineered to express a TnMUC1-Targeted Genetically-Modified Chimeric Antigen (CAR)
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1
Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-TnMUC1
Mayo Clinic of Arizona
Phoenix, Arizona, United States
The Angeles Clinic and Research Institute
Los Angeles, California, United States
Moffitt Cancer Center
Tampa, Florida, United States
University of Chicago Medical Center
Chicago, Illinois, United States
Washington University School of Medicine
St Louis, Missouri, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
University of Washington Medical Center
Seattle, Washington, United States
Dose Escalation: Dose Identification of CART-TnMUC1
Incidence of Dose Limiting Toxicity (DLT) in solid tumors and multiple myeloma
Time frame: Up to 2 years
Cohort Expansion: Objective Response in solid tumors
Proportion of patients having a confirmed Complete Response (CR) or Partial Response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to 2 years
Safety of CART-TnMUC1 in solid tumors and multiple myeloma
Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and by severity Grade
Time frame: Up to 2 years
Tolerability of CART-TnMUC1 in solid tumors and multiple myeloma
Frequency of treatment emergent AEs, frequency of clinical changes from baseline in vital signs, changes in electrocardiogram, and hematology and chemistry laboratory shifts from baseline
Time frame: Up to 2 years
Feasibility of CART-TnMUC1 in solid tumors and multiple myeloma
Proportion of enrolled patients who did not receive CART-TnMUC1 cells
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Overall Survival (OS) in solid tumors and multiple myeloma
OS as defined by the interval between CART-TnMUC1 cell infusion and date of death by any cause
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Progression Free Survival (PFS) in solid tumors
PFS as defined by the interval between CART-TnMUC1 cell infusion and date of disease progression by RECIST v1.1 or death in solid tumors and by International Myeloma Working Group (IMWG) criteria in multiple myeloma
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Objective Response Rate (ORR) in solid tumors and multiple myeloma
Proportion of patients having a confirmed CR or PR per RECIST v1.1 in solid tumors and IMWG criteria (PR, Very Good PR, CR, Stringent CR) in multiple myeloma
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Clinical Benefit Rate in solid tumors
Proportion of patients having a confirmed CR, PR, or Stable Disease (SD) per RECIST v1.1
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Duration of Response (DOR) in solid tumors and multiple myeloma
DOR as defined by the interval of first documented response until first documented disease progression or death in solid tumors and multiple myeloma
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Time to Response (TTR) in solid tumors and multiple myeloma
Time to Response as defined by the interval between CART-TnMUC1 cell infusion and first documented CR or PR per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Time to Progression (TTP) in multiple myeloma
Time to Progression as defined by the interval between CART-TnMUC1 cell infusion and first documented progression or death due to disease per RECIST v1.1 in solid tumors and IMWG criteria in multiple myeloma
Time frame: Up to 2 years
Preliminary anti-tumor efficacy of CART as assessed by Minimal Residual Disease (MRD) in multiple myeloma
Defined by MRD-negative rate per IMWG criteria
Time frame: Up to 2 years
Peripheral expansion and persistence of CART-TnMUC1 cells in solid tumors and multiple myeloma
Defined as quantitative polymerase chain reaction (qPCR) documenting loss of CART cells
Time frame: Up to 15 years
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