A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer

Phase 2TerminatedNCT05451849

TCR2 Therapeutics14 enrolled

Overview

TC-510 is a novel cell therapy that consists of autologous genetically engineered T cells expressing two synthetic constructs: first, 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 and second, a PD-1:CD28 switch receptor, which is expressed on the surface of the T cell, independently from the TCR. The PD-1:CD28 switch receptor comprises the PD-1 extracellular domain fused to the CD28 intracellular domain via a transmembrane domain. Thus, the switch is designed to produce a costimulatory signal upon engagement with PD-L1 on cancer cells.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mesothelioma Mesotheliomas Pleural Mesothelioma, Malignant Mesothelioma Peritoneum

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Patient is \> 18 years of age at the time the Informed Consent is signed. * Patient has a pathologically confirmed diagnosis of either MPM, Serous Ovarian Adenocarcinoma, Pancreatic Adenocarcinoma, TNBC, and Colorectal Cancer * Patient's tumor has been reviewed with confirmed positive MSLN expression on \>/= 50% of tumor cells that are 1+, 2+ and/or 3+ by immunohistochemistry. Patients with epithelioid MPM, confirmation of MSLN expression is not required prior to enrollment. * Prior to TC-510 infusion, patients must have received at least 1 but no more than 5 systemic therapies for metastatic or unresectable disease with more details provided in the protocol * Patients has an ECOG performance status 0 or 1 * 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 Exclusion Criteria: * Inability to follow the procedures of the study * Known or suspected non-compliance, drug, or alcohol use

Locations (7)

University of California, San Francisco

San Franciso, California, United States

University of Miami

Miami, Florida, United States

National Cancer Institute

Bethesda, Maryland, United States

University of Minnesota, Masonic Cancer Center

Minneapolis, Minnesota, United States

Montefiore Einstein Cancer Center

The Bronx, New York, United States

University of Oklahoma

Oklahoma City, Oklahoma, United States

SCRI Oncology Partners

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAEs

TEAEs are defined as AEs that were reported or worsened on or after the first administration of protocol-defined lymphodepleting chemotherapy through 3 months after the last infusion of TC-510. To be defined as serious, the event met at least one of the following serious criteria: * Fatal * Life-threatening (places the patient at immediate risk of death) * Requires in-patient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Congenital anomaly/birth defect * Other medically important serious event

Time frame: From start of lymphodepleting chemotherapy through end of the interventional phase (up to approximately 38 months)

Secondary Outcomes

Overall Response Rate (ORR)

ORR is the proportion of patients with a Complete Response (CR) or Partial Response (PR) via independently reviewed RECIST v 1.1 relative to the total number of patients in the mITT population.

Time frame: From first TC-510 infusion through study completion (up to approximately 38 months)

Disease Control Rate (DCR)

DCR is defined as the ORR plus the proportion of patients with Stable Disease (SD) for at least 8 weeks via independently reviewed RECIST v 1.1 relative to the total number of patients in the mITT population.