NCT03907852

Brief Summary

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.

Trial Health

78
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P50-P75 for phase_1

Timeline
30mo left

Started Apr 2019

Longer than P75 for phase_1

Geographic Reach
2 countries

11 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress74%
Apr 2019Nov 2028

First Submitted

Initial submission to the registry

April 1, 2019

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 9, 2019

Completed
6 days until next milestone

Study Start

First participant enrolled

April 15, 2019

Completed
5.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 19, 2024

Completed
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 2, 2028

Expected
Last Updated

August 27, 2025

Status Verified

August 1, 2025

Enrollment Period

5.6 years

First QC Date

April 1, 2019

Last Update Submit

August 20, 2025

Conditions

Outcome Measures

Primary Outcomes (2)

  • Phase 1- Primary Objective

    Establish the recommended Phase 2 dose (RP2D) according to dose-limiting toxicity (DLT) of defined adverse events.

    DLTs within 28 days post-treatment

  • Phase 2- Primary Objective

    To evaluate the efficacy of autologous genetically modified T cells (gavo-cel), with or without immuno-oncology agents, in patients with MSLN-expressing unresectable, metastatic, or recurrent cancers as determined by overall response rate and disease control rate using RECIST v1.1 (or mesothelioma-specific RECIST criteria, if applicable).

    ORR at 3 months; DCR based on ORR + SD lasting at least 8 weeks

Study Arms (3)

Lymphodepletion followed by gavo-cel

EXPERIMENTAL

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

Biological: gavo-celDrug: fludarabineDrug: cyclophosphamide

Lymphodepletion followed by gavo-cel plus nivolumab

EXPERIMENTAL

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

Biological: gavo-celDrug: fludarabineDrug: cyclophosphamideDrug: Nivolumab

Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

EXPERIMENTAL

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

Biological: gavo-celDrug: fludarabineDrug: cyclophosphamideDrug: NivolumabDrug: Ipilimumab

Interventions

gavo-celBIOLOGICAL

gavo-cel

Lymphodepletion followed by gavo-celLymphodepletion followed by gavo-cel plus nivolumabLymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

lymphodepletion chemotherapy

Lymphodepletion followed by gavo-celLymphodepletion followed by gavo-cel plus nivolumabLymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

lymphodepletion chemotherapy

Lymphodepletion followed by gavo-celLymphodepletion followed by gavo-cel plus nivolumabLymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

immuno-oncology agent

Lymphodepletion followed by gavo-cel plus nivolumabLymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

immuno-oncology agent

Lymphodepletion followed by gavo-cel plus nivolumab and ipilimumab

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (11)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

University of Miami Sylvester Cancer Center

Miami, Florida, 33136, United States

Location

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

National Cancer Institute

Bethesda, Maryland, 20814, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2C1, Canada

Location

Related Publications (1)

  • Hassan R, Butler M, O'Cearbhaill RE, Oh DY, Johnson M, Zikaras K, Smalley M, Ross M, Tanyi JL, Ghafoor A, Shah NN, Saboury B, Cao L, Quintas-Cardama A, Hong D. Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results. Nat Med. 2023 Aug;29(8):2099-2109. doi: 10.1038/s41591-023-02452-y. Epub 2023 Jul 27.

MeSH Terms

Conditions

MesotheliomaMesothelioma, MalignantCholangiocarcinomaOvarian NeoplasmsCarcinoma, Non-Small-Cell Lung

Interventions

fludarabineCyclophosphamideNivolumabIpilimumab

Condition Hierarchy (Ancestors)

AdenomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms, MesothelialLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SitePleural NeoplasmsLung DiseasesRespiratory Tract DiseasesAdenocarcinomaCarcinomaEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinoma, BronchogenicBronchial Neoplasms

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsAntibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 1, 2019

First Posted

April 9, 2019

Study Start

April 15, 2019

Primary Completion

November 19, 2024

Study Completion (Estimated)

November 2, 2028

Last Updated

August 27, 2025

Record last verified: 2025-08

Locations