FDA Grants Orphan Drug Status to Gavocabtagene Autoleucel for Cholangiocarcinoma


The FDA has granted an orphan drug designation to gavocabtagene autoleucel as a potential treatment for patients with cholangiocarcinoma.

The FDA has granted an orphan drug designation to gavocabtagene autoleucel (gavo-cel; TC-210) as a potential treatment for patients with cholangiocarcinoma, according to TCR2 Therapeutics.1

Gavo-cel, a novel, autologous cell therapy defined as T-cell receptor (TCR) fusion construct T cells (TRuC-T cells), is currently being evaluated in a phase 1/2 trial (NCT03907852) of patients with treatment-refractory mesothelin-expressing solid tumors. The findings will be presented at the 2021 ESMO Congress, and will comprise data from patients with malignant mesothelioma, ovarian cancer, and cholangiocarcinoma.

Mesothelin is described as a cell-surface glycoprotein highly expressed in several solid malignancies, including malignant pleural/peritoneal mesothelioma, ovarian cancer, cholangiocarcinoma, breast cancer, and pancreatic cancer. Moreover, mesothelin overexpression is linked with worse prognosis in select tumors; it has an active role in malignant transformation and tumor aggressiveness via promotion of cancer cell proliferation, invasion, and metastasis.

Non–small cell lung cancers (NSCLCs), ovarian cancers, mesotheliomas and cholangiocarcinomas that express mesothelin comprise 80,000 patients in the United States each year.

Gavo-cel is described as autologous genetically engineered T cells that express a single-domain antibody with the ability to recognize human mesothelin that is fused to CD3-epsilon subunit; this is incorporated into the endogenous T-cell receptor complex.

Preclinical data showed that TRuC-T cells demonstrated encouraging activity compared with CAR T-cell therapy, while secreting lower levels of cytokine release.

In the ongoing, phase 1/2 trial, investigators sought to determine the recommended phase 2 dose (RP2D) of gavo-cel (phase 1 portion) as well as the overall response rate (ORR; phase 2) in approximately 70 patients with advanced mesothelin-expressing, unresectable, metastatic, or recurrent cancers. As part of a lymphodepletion regimen, fludarabine will be administered at 30 mg/m2 daily on days -7 through -4 and cyclophosphamide at 600 mg/m2 daily on days -6 through -4 followed by gavo-cel.

To be eligible for enrollment, patients aged 18 years or older must have a confirmed diagnosis of malignant pleural/peritoneal mesothelioma, serous ovarian adenocarcinoma, cholangiocarcinoma, or NSCLC; have mesothelin expression on more than 50% of tumor cells that are immunohistochemistry 2+ and/or 3+; must have received at least 1 systemic standard treatment for metastatic or unresectable disease; an ECOG performance status of 0 or 1; a left ventricular ejection fraction greater than 45%; fit for leukapheresis and has adequate venous access for cell collection; and must have adequate organ function.

In December 2020, TCR2 Therapeutics announced interim findings from the phase 1 portion of the trial.3 As of the data cutoff date of November 24, 2020, which had data from the first 8 patients, results showed that there were 3 partial responses (PRs) via RECIST v1.1 criteria. The first patient with ovarian cancer on study achieved a confirmed PR up until 6 months.

Additional data showed that the first patient who received gavo-cel at a higher dose, 1 x 108/m2, without lymphodepletion had stable disease for 2 months and did not experience significant toxicities. There were also reports of TRuC-T cell expansion and cytokine induction in all patients.

Regarding safety, 2 patients as of the data cutoff data reported treatment-related non-hematologic toxicities that were higher than grade 2; there was no evidence of neurotoxicity nor on-target/off-tumor toxicity.

TC-110, another TRuC-T cell product, is being studied in an ongoing phase 1/2 trial of adult patients with CD19-positive acute lymphoblastic leukemia and with aggressive or indolent non-Hodgkin lymphoma.


  1. TCR² Therapeutics Receives FDA Orphan Drug Designation for Gavo-cel for the Treatment of Cholangiocarcinoma. News release. TCR2 Therapeutics. September 2, 2021. Accessed September 2, 2021. https://bit.ly/2V8GibVA
  2. Phase 1/2 Single Arm Open-Label Clinical Trial of Gavocabtagene Autoleucel (Gavo-cel) in Patients With Advanced Mesothelin-Expressing Cancer. ClinicalTrials.gov. Updated June 29, 2021. Accessed September 2, 2021. https://clinicaltrials.gov/ct2/show/NCT03907852
  3. TCR² Announces RECIST Response in Ovarian Cancer from Ongoing Phase 1/2 Trial of Tc-210 in Treatment Refractory Mesothelin-Expressing Solid Tumors. News release. TCR2 Therapeutics. December 13, 2020. Accessed September 2, 2021. https://bit.ly/2WHdV58
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