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.
Brief Title
A Phase 1/2 Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer
Categories
Completion Date
Completion Date Type
Estimated
Conditions
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
Eligibility Criteria
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
* 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
Inclusion Criteria
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
* 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
Gender
All
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05451849
Org Class
Industry
Org Full Name
TCR2 Therapeutics
Org Study Id
TCR2-21-01
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
A Phase 1/2 Single Arm Open-Label Clinical Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer
Primary Outcomes
Outcome Description
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
Outcome Measure
Phase 1 - Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.
Outcome Time Frame
DLTs within 28 days post-treatment
Outcome Description
ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1
Outcome Measure
Phase 2 - Overall Response Rate (ORR)
Outcome Time Frame
Up to 2 years post-treatment
Outcome Description
DCR defined as a composite of ORR and stable disease (SD) lasting at least 8 weeks.
Outcome Measure
Phase 2 - Disease Control Rate (DCR)
Outcome Time Frame
Up to 2 years post-treatment
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Roberto Alejandro Sica
Investigator Email
asica@montefiore.org