A few days ago, TCR²Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Gavo-cel Orphan Drug Designation (ODD) for the treatment of cholangiocarcinoma.

Gavo-cel is a new type of cell therapy consisting of autologous genetically engineered T cells expressing a single domain antibody that can recognize human mesothelin and fused with the CD3-ε subunit, which is integrated into the endogenous after expression Sex T cell receptor (TCR) complex. The purpose of this phase 1/2 trial is to determine the recommended phase 2 dose (RP2D) and the overall response rate of this therapy in mesothelin-expressing advanced cancer patients.

Mesothelin is a cell surface glycoprotein that is highly expressed in a variety of solid tumors, including malignant pleural/peritoneal mesothelioma, ovarian cancer, cholangiocarcinoma, breast cancer, and pancreatic cancer. Because it can promote the proliferation, invasion and metastasis of cancer cells, mesothelin plays an active role in malignant transformation and tumor invasion. In addition, the overexpression of mesothelin is associated with the poor prognosis of certain cancers. Among the various solid tumors expressing mesothelin, in the United States alone, there are as many as 80,000 patients with non-small cell lung cancer, ovarian cancer, mesothelioma, and cholangiocarcinoma each year.

TCR² proprietary T cell receptor (TCR) Fusion Construct T cells (TRuC-T cells) can specifically recognize and kill cancer cells by using signals from the entire TCR, independent of human leukocyte antigen (HLA). In preclinical studies, compared with chimeric antigen receptor T cells (CAR-T cells), TRuC-T cells show superior anti-tumor activity, while secreting and releasing fewer cytokines.

The company's TRuC-T cell candidate product Gavo-cel targeting solid tumors is currently being studied in phase 1/2 clinical trials to treat mesothelin-positive non-small cell lung cancer (NSCLC), ovarian cancer, and malignant pleura/peritoneum Mesothelioma and cholangiocarcinoma. The company's other TRuC-T cell candidate product for hematological malignancies, TC-110, is currently being studied in a phase 1/2 clinical trial to treat CD19-positive adult acute lymphoblastic leukemia (aALL) and aggressive or indolent non- Patients with Hodgkin's Lymphoma (NHL).

According to the previously published phase 1 trial data, Gavo-cel is safe and well tolerated. No patients had neurotoxicity or target toxicity in normal tissues, and 2 patients had a cytokine release syndrome greater than grade 3. (CRS), and used touzumab and glucocorticoid therapy. All 8 patients underwent at least one disease remission assessment, the disease control rate (DCR) was 100%, all patients experienced tumor regression, and the median diameter of the target lesions dropped to 43% (Range: 5%-75 %). Under the RECIST v1.1 standard, the ORR was 38%, 2 cases of confirmed partial remission (PR) and 1 case of unconfirmed PR, including 1 patient with ovarian cancer who achieved PR and a new lesion appeared again within 6 months.

Part of the data from the Phase 1/2 dose-escalation clinical trial of Gavo-cel (TC-210) for the treatment of patients with refractory mesothelin-expressing solid tumors will be highlighted as part of the oral report of the European Society of Medical Oncology on September 17 , Including the efficacy of gavo-cel in malignant mesothelioma, ovarian cancer and cholangiocarcinoma.