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

NCT05451849 — Phase 1 / Phase 2, Terminated, 14 participants, TCR2 Therapeutics
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A Phase 1/2 Single Arm Open-Label Clinical Trial of TC-510 In Patients With Advanced Mesothelin-Expressing Cancer

RegistryNCT05451849
StatusTerminated - No participants were enrolled in Phase 2 as Phase I was terminated early due to the lack of a clear signal of robust clinical activity.
PhasePhase 1 / Phase 2
Study typeInterventional; na, single group, masking: none, treatment
Enrollment14 (Actual)
SponsorTCR2 Therapeutics (Industry)
ConditionsMesothelioma, 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
InterventionsTC-510, Fludarabine, Cyclophosphamide (Biological, drug)
Datesstart 2022-06-21, primary completion 2025-08-30, completion 2025-08-30, first posted 2022-07-11, last updated 2026-07-13
Locations7 sites in United States

Related Papers Related Patents Related Grants Related Experts
All trials for Mesothelioma All trials for Mesotheliomas Pleural All trials of TC-510 All trials of Fludarabine

-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.

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+Arms and interventions

ArmTypeInterventionsDescription
Lymphodepletion followed by TC-510ExperimentalBiological: TC-510; Drug: Fludarabine; Drug: CyclophosphamideLymphodepletion (fludarabine and cyclophosphamide) followed by TC-510 T cells
  • TC-510 (Biological): TC-510
  • Fludarabine (Drug): Fludarabine
  • Cyclophosphamide (Drug): Cyclophosphamide

+Outcome measures

Primary outcomes

  • 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 outcomes

  • 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.

+Eligibility

Sex: All, ages: 18 Years to any

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

+Posted results

Participant flow

MilestonePhase 1
Started14
Completed6
Not completed8

Outcome results

  • Number of Participants With Treatment Emergent Adverse Events (TEAE) and Serious TEAEs (Primary), Count of participants, Participants: Phase 1 6
  • Overall Response Rate (ORR) (Secondary), Count of participants, Participants: Phase 1 1
  • Disease Control Rate (DCR) (Secondary), Count of participants, Participants: Phase 1 2

Adverse events

Time frame: From start of lymphodepleting chemotherapy through end of the interventional phase (up to approximately 38 months)

ArmDeathsSerious adverse eventsOther adverse events
Phase 11/6 (16.7%)4/6 (66.7%)6/6 (100.0%)

Serious adverse events by term

TermOrgan systemPhase 1
Cytokine Release SyndromeImmune system disorders2/6
PneumonitisImmune system disorders2/6
HypoxiaRespiratory, thoracic and mediastinal disorders1/6

Other adverse events by term

TermOrgan systemPhase 1
Cytokine Release SyndromeImmune system disorders5/6
HypoxiaRespiratory, thoracic and mediastinal disorders3/6
Pleuritic PainRespiratory, thoracic and mediastinal disorders3/6
PneumonitisRespiratory, thoracic and mediastinal disorders3/6
CoughRespiratory, thoracic and mediastinal disorders1/6
DypsnoeaRespiratory, thoracic and mediastinal disorders1/6
Alanine aminotransferase increasedInvestigations2/6
Aspartate aminotransferas increasedInvestigations2/6
Lipase increasedInvestigations2/6
Amylase increasedInvestigations1/6
Blood alkaline phosphatase increasedInvestigations1/6
Platelet count decreasedInvestigations1/6
Troponin I increasedInvestigations1/6
Abdominal painGastrointestinal disorders1/6
PancreatitisGastrointestinal disorders1/6
Dry eyeEye disorders1/6
FatigueGeneral disorders1/6
HypotensionVascular disorders1/6
PalpitationsCardiac disorders1/6
Sinus tachycardiaCardiac disorders1/6

Limitations and caveats: Due to the lack of a clear signal of robust clinical activity during Phase 1, the study was terminated early and Phase 2 was not initiated. Dose-limiting toxicity and recommended Phase 2 dose determination were not performed.

+Locations (7)

FacilityCityCountryStatus
University of California, San FranciscoSan Franciso, CaliforniaUnited States
University of MiamiMiami, FloridaUnited States
National Cancer InstituteBethesda, MarylandUnited States
University of Minnesota, Masonic Cancer CenterMinneapolis, MinnesotaUnited States
Montefiore Einstein Cancer CenterThe Bronx, New YorkUnited States
University of OklahomaOklahoma City, OklahomaUnited States
SCRI Oncology PartnersNashville, TennesseeUnited States

+Study documents