Mesothelin is a cell surface glycoprotein that is highly expressed in a variety of solid malignancies, including malignant pleural/peritoneal mesothelioma, ovarian cancer, cholangiocarcinoma, breast cancer, and pancreatic cancer. In addition, in some tumors, mesothelin overexpression is associated with poor prognosis; it plays an active role in malignant transformation and tumor invasion by promoting cancer cell proliferation, invasion, and metastasis. In the United States, mesothelin causes 80,000 cases of non-small cell lung cancer (NSCLCs), ovarian cancer, mesothelioma, and cholangiocarcinoma every year.
(Source: Internet)
TCR2 Therapeutics said the FDA has granted orphan drug designation to gavocabtagene autoleuel (gavo-cel; TC-210) as a potential treatment for patients with cholangiocarcinoma.
Gavo-cel is a novel autologous cell therapy defined as T-cell receptor (TCR) fusion-constructed T cells (TRuC-T cells) that is currently in a Phase 1/2 clinical trial (NCT03907852) for the treatment of patients with refractory mesothelin-expressing solid tumors. The findings will be presented at ESMO 2021 and will include data from patients with malignant mesothelioma, ovarian cancer and cholangiocarcinoma.
Preclinical data show that TRuC-T cells exhibit encouraging activity while secreting lower levels of cytokine release compared to CAR-T cell therapy.
In the ongoing Phase 1/2 trial, investigators are seeking to determine the recommended Phase 2 dose (RP2D) of gavo-cel (Phase 1 part) and overall response rate (ORR; Phase 2) in approximately 70 patients with advanced mesothelin-expressing, unresectable, metastatic or recurrent cancer. As part of the lymphodepletion regimen, fludarabine 30 mg/m2 daily on days -7 to -4 and cyclophosphamide 600 mg/m2 daily on days -6 to -4 were administered followed by gavo-cel.
In December 2020, TCR2 Therapeutics announced the interim results of the Phase 1 trial. As of November 24, 2020, based on trial data from the first 8 patients, the results showed that 3 patients had achieved partial response (according to RECIST v1.1 criteria). The first patient with ovarian cancer in the trial achieved a definite partial response at six months.
Other data showed that the first patient who received a higher dose of gavo-cel (1×108/m2) (without lymphocyte depletion) had stable disease for 2 months without obvious toxic effects. TRuC-T cell expansion and cytokine induction were also reported in all patients.
TC-110 is another TRuC-T cell product currently in Phase 1/2 clinical trials in adult patients with CD19-positive acute lymphoblastic leukemia and aggressive or indolent non-Hodgkin lymphoma.
References:
https://www.onclive.com/view/fda-grants-orphan-drug-status-to-gavocabtagene-autoleucel-for-cholangiocarcinoma
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