FDA Grants Orphan Drug Status to Gavocabtagene Autoleucel for Cholangiocacinoma Treatment


Gavocabtagene autoleucel has been granted orphan drug designation from the FDA and is being investigated in other solid tumors in a phase 1/2 clinical trial.

The FDA has granted orphan drug designation to gavocabtagene autoleucel (TC-210; gavo-cel) for the treatment of cholangiocarcinoma, according to a press release from the developer, TCR2 Therapeutics, Inc.1

Gavo-cel is in investigational therapy consisting of autologous genetically engineered T cells. The cells express a single-domain antibody that enables mesothelin overexpression to be recognized.

In an ongoing phase 1/2 study, gavo-cel has begun to demonstrate promise for the treatment of patients with treatment-refractory mesothelin-expressing solid tumors, including cholangiocarcinoma. The agent showed tumor regression in all patients treated and demonstrated a manageable safety profile.2

The single-arm, open-label study (NCT03907852) is aiming to establish the recommended phase 2 dose of gavo-cel in phase 1 and efficacy determined by overall response rate (ORR) per RECIST v1.1 of gavo-cel in phase 2. The exploratory end points of the study include the expansion, persistence, phenotype, functionality of T cells, cytokine levels, and immunogenicity the gavo-cel.

Gavo-cel treatment is initially administered at 4 different dose levels., Thus far, 1 patient has received gavo-cel 5 x 107 cells/m2 and 1 patient has received the agent at 1 x 108 cell/m2. Three patients in cohort 3 received dose levels for 4 with lymphodepletion and without lymphodepletion, respectively. In cohort 4, 3 patients received gavo-cel at dose level 7 and 8 with or without lymphodepletion.

To be included in the study, patients are required to be at least 18 years of age with a pathologically confirmed diagnosis of malignant pleural/peritoneal mesothelioma (MPM), serous ovarian adenocarcinoma, cholangiocarcinoma, or non-small cell lung cancer (NSCLC), an ECOG performance status of 0 or 1, adequate organ function, and adequate screening test results at baseline. Before being treated with gavo-cel in the study, patients must have received at least 1 systemic standard of care therapy for metastatic or unresectable disease.

In the phase 2 expansion cohort, 12 patients with NSCLC, 10 patients with ovarian cancer, 10 patients with cholangiocarcinoma, and 10 patients with MPM were included. Baseline characteristics were available for 8 patients, showing a median age of 64.5 years (range, 36-84 years) and a median of 5.5 prior therapies (range, 2-9 therapies).

Among those treated at dose level 1, partial responses (PRs) and stable disease (SD) were achieved in 11 and 10 patients, respectively. Sd was also observed in the 8 patients treated at dose level 2.

In all patients analyzed (n = 8), the ORR was 38% and the disease control rate was 100%. In the 6 patients who had gavo-cel with lymphodepletion, the ORR was 50% and the DCR was 100%.

Treatment-emergent adverse events (TEAEs) included neutropenia (75%), lymphopenia (88%), and thrombocytopenia (25%). The AE of special interest in the study was cytokine release syndrome observed in 25% of patients. Infections of pneumonitis and sepsis were also seen in 1 patient each.

Updated data from the phase 1/2 study will be presented during the upcoming European Society for Medical Oncology Congress 2021, TCR2 Therapeutics announced, in the press release.


1. TCR² Therapeutics receives fda orphan drug designation for gavo-cel for the treatment of cholangiocarcinoma. New release. TCR² Therapeutics. September 2, 2021. Accessed September 2, 2021. https://bit.ly/2WM7EW4

2. Powering the TCRr to transform the live of cancer patient with solid tumors. TCR2 Therapeutics website. Accessed Septmeber 2, 2021. https://bit.ly/3gSM8py

3. Phase 1/2 Trial of gavo-cel (TC-210) in patients with advanced mesothelin-expressing cancer. Clinicaltrials.gov. Accessed September 2, 2021. https://bit.ly/3kN8cDl

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