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

TCR2 Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Ovarian Neoplasms; TNBC - Triple-Negative Breast Cancer; Pancreatic Adenocarcinoma; Cholangiocarcinoma; Non Small Cell Lung Cancer; Mesothelioma, Malignant; Ovarian Adenocarcinoma; Ovarian Cancer; Mesothelioma Peritoneum; Colorectal Neoplasms; Mesothelioma; Triple Negative Breast Cancer; Mesotheliomas Pleural; Pancreatic Neoplasms; Colorectal Cancer; Pancreatic Cancer; Ovarian Serous Adenocarcinoma

Treatments: Biological: TC-510; Drug: Fludarabine; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT05451849

TCR2-21-01

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Lymphodepletion followed by TC-510

Experimental group

Description:

Lymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells

Treatment:

Drug: Fludarabine

Drug: Cyclophosphamide

Biological: TC-510