FDA Grants Orphan Drug Status to Gavocabtagene Autoleucel for Cholangiocacinoma Treatment

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.

_References:

_{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}