Cholangiocarcinoma, Colorectal Cancer, Colorectal Neoplasms, Mesothelioma, Mesothelioma, Malignant, Mesothelioma Peritoneum, Mesotheliomas Pleural, Non Small Cell Lung Cancer, Ovarian Adenocarcinoma, Ovarian Cancer, Ovarian Neoplasms, Ovarian Serous Adenocarcinoma, Pancreatic Adenocarcinoma, Pancreatic Cancer, Pancreatic Neoplasms, TNBC - Triple-Negative Breast Cancer, Triple Negative Breast Cancer
Conditions
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.
Interventions
BIOLOGICALTC-510
TC-510
DRUGFludarabine
Fludarabine
DRUGCyclophosphamide
Cyclophosphamide
Sponsors
TCR2 Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAEs | From start of lymphodepleting chemotherapy through end of the interventional phase (up to approximately 38 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From first TC-510 infusion through study completion (up to approximately 38 months) | 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. |
| Disease Control Rate (DCR) | From first TC-510 infusion through study completion (up to approximately 38 months) | 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. |
Countries
United States
Participant flow
Pre-assignment details
Fourteen (14) participants were screened and subsequently underwent leukapheresis in Phase 1 (Intent-to-Treat population). Six (6) participants received lymphodepleting chemotherapy and were dosed in Phase 1 (modified Intent-to-Treat population). No participants were subsequently included in Phase 2 as Phase I was terminated early due to the lack of a clear signal of robust clinical activity.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized Mean Age | 54 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 6 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 2 Participants |
| Tumor type MPM | 3 Participants |
| Tumor type Ovarian | 1 Participants |
| Tumor type Pancreatic | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 6 |
| other Total, other adverse events | 6 / 6 |
| serious Total, serious adverse events | 4 / 6 |
Outcome results
None listed