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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase 1/2 Single Arm Open-Label Clinical Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer

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

Intervention / Treatment
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* Biological: TC-510
* Drug: Fludarabine
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lymphodepletion followed by TC-510<br>Lymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells | Biological: TC-510<br>* TC-510<br>Drug: Fludarabine<br>* Fludarabine<br>Drug: Cyclophosphamide<br>* Cyclophosphamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 - Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events. | 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 | DLTs within 28 days post-treatment | 
| Phase 2 - Overall Response Rate (ORR) | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 | Up to 2 years post-treatment | 
| Phase 2 - Disease Control Rate (DCR) | DCR defined as a composite of ORR and stable disease (SD) lasting at least 8 weeks. | Up to 2 years post-treatment |