Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer

TCR2 Therapeutics

Status and phase: Active, not recruiting; Phase 2; Phase 1

Conditions: Non Small Cell Lung Cancer Metastatic; High Grade Ovarian Serous Adenocarcinoma; Mesothelioma Peritoneum; Mesothelioma; Pleura; Cholangiocarcinoma Recurrent; Cholangiocarcinoma; Mesothelioma, Malignant; Non Small Cell Lung Cancer; Mesothelioma; Ovarian Cancer; Mesotheliomas Pleural

Treatments: Drug: cyclophosphamide; Drug: fludarabine; Biological: gavo-cel; Drug: Nivolumab; Drug: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT03907852

TCR2-18-01

Details and patient eligibility

About

Gavocabtagene autoleucel (gavo-cel; TC-210) is a novel cell therapy that consists of autologous genetically engineered T cells expressing 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.

This Phase 1/2 study aims to establish the recommended Phase 2 dose (RP2D) and subsequently evaluate the efficacy of gavo-cel, with and without immuno-oncology agents, in patients with advanced mesothelin-expressing cancers, with overall response rate and disease control rate as the primary Phase 2 endpoints.

Enrollment: 57 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Patient is at least 18 years of age at the time the Informed Consent is signed.
• Patient has a pathologically confirmed diagnosis of either Malignant Pleural/Peritoneal Mesothelioma (MPM), Serous Ovarian Adenocarcinoma, Cholangiocarcinoma, or Non-Small Cell Lung Cancer (NSCLC) at screening.
• Patient's tumor has been pathologically reviewed by the central laboratory. For Serous Ovarian Adenocarcinoma, patients must have confirmed positive MSLN expression on >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by immunohistochemistry (IHC). Ovarian patients will subsequently be stratified into two groups: high MSLN expression (>/= 50% of tumor cells that are 2+ and/or 3+) or low MSLN expression (>/= 30% of tumor cells that are 1+, 2+, and/or 3+ not meeting criteria for the high MSLN expression group). MPM patients must have MSLN expression of >/= 50% of tumor cells that are 2+ and/or 3+ by IHC. Cholangiocarcinoma and NSCLC patients must have MSLN expression of >/= 30% of tumor cells that are 1+, 2+, and/or 3+ by IHC.
• Prior to gavo-cel infusion, patients must have received at least 1 systemic standard of care therapy for metastatic or unresectable disease, with the exception of Cholangiocarcinoma patients who may have elected not to pursue standard frontline therapy. Regardless of tumor type, patients must not exceed 5 prior lines of therapy (excluding bridging therapy and surgical procedures). More details provided in the clinical protocol.
• Patient has an Eastern Cooperative Oncology Group performance status 0 or 1.
• Patient has a left ventricular ejection fraction > 45% as measured by resting echocardiogram, with no clinically significant pericardial effusion.
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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57 participants in 3 patient groups

Lymphodepletion followed by gavo-cel

Experimental group

Description:

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel

Treatment:

Drug: fludarabine

Biological: gavo-cel

Drug: cyclophosphamide

Lymphodepletion followed by gavo-cel plus nivolumab

Experimental group

Description:

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel

Treatment:

Drug: Nivolumab

Drug: fludarabine

Biological: gavo-cel

Drug: cyclophosphamide

Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

Experimental group

Description:

fludarabine 30 mg/m2/d on days -7 through -4 and cyclophosphamide 600 mg/m2/d on days -6 through -4 followed by gavo-cel with nivolumab 360mg every 3 weeks starting on Day 21 post gavo-cel and ipilimumab 1mg/kg every 6 weeks starting on Day 42 post gavo-cel

Treatment:

Drug: Ipilimumab

Drug: Nivolumab

Drug: fludarabine

Biological: gavo-cel

Drug: cyclophosphamide