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

Phase 1

Active, not recruiting

• Conditions: Mesothelioma; Mesothelioma, Malignant; Ovarian Cancer; Pancreatic Cancer; TNBC - Triple-Negative Breast Cancer; Ovarian Adenocarcinoma; Ovarian Neoplasms; Mesotheliomas Pleural; Colorectal Cancer; Triple Negative Breast Cancer
• Interventions: Biological: TC-510; Drug: Fludarabine; Drug: Cyclophosphamide

• Registration Number: NCT05451849
• Lead Sponsor: TCR2 Therapeutics

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2022-06-21
• Study First Submitted: 2022-06-21
• Study First Submitted QC: 2022-07-06
• Study First Posted: 2022-07-11
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-06
• Primary Completion: 2028-10-30
• Study Completion: 2028-10-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 6

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

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Exclusion Criteria

• Inability to follow the procedures of the study
• Known or suspected non-compliance, drug, or alcohol use

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Lymphodepletion followed by TC-510	TC-510	Lymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells
Lymphodepletion followed by TC-510	Cyclophosphamide	Lymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells
Lymphodepletion followed by TC-510	Fludarabine	Lymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells

Primary Outcome Measures

Name	Time	Method
Phase 1 - Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.	DLTs within 28 days post-treatment	Phase 1 -The number and percent of patients in the DLT evaluable set who experienced DLTs from the first administration of study drug up to 28 days post study drug treatment will be summarized by dosing group
Phase 2 - Overall Response Rate (ORR)	Up to 2 years post-treatment	ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
Phase 2 - Disease Control Rate (DCR)	Up to 2 years post-treatment	DCR defined as a composite of ORR and stable disease (SD) lasting at least 8 weeks.

Trial Locations

Locations (7)

University of Miami; 🇺🇸 Miami, Florida, United States

University of Minnesota, Masonic Cancer Center; 🇺🇸 Minneapolis, Minnesota, United States

University of Oklahoma; 🇺🇸 Oklahoma City, Oklahoma, United States

University of California, San Francisco; 🇺🇸 San Francisco, California, United States

National Cancer Institute; 🇺🇸 Bethesda, Maryland, United States

SCRI Oncology Partners; 🇺🇸 Nashville, Tennessee, United States

Montefiore Einstein Cancer Center; 🇺🇸 Bronx, New York, United States