CARsgen Therapeutics’ novel pipeline therapy for advanced hepatocellular carcinoma (HCC) stands out in the American Society of Clinical Oncology (ASCO) virtual annual meeting for being the first-in-class approach with a unique mechanism of action that targets heavily pretreated advanced HCC patients, says GlobalData, a leading data and analytics company.

Results for multiple HCC clinical trials were presented at the 2021 ASCO virtual annual meeting. CARsgen presented data from a Phase I trial (NCT03980288) of its fourth-generation chimeric antigen receptor T (CAR-T) cells targeting glypican-3 (GPC3). Fourth-generation CAR-T cells are additionally engineered to secrete a transgenic cytokine upon CAR signaling in the targeted tumor tissue. As a result, in addition to the direct antitumor attack, they can trigger T cells to eliminate antigen-negative cancer cells at the target site. GPC3 is a cell-surface glycoprotein that is highly expressed in HCC and is thus being evaluated as a target for HCC immunotherapy.

In this study, CARSgen’s fourth-generation CAR-GPC3 T cells in combination with the tyrosine kinase inhibitors (TKIs) Nexavar (sorafenib) or Stivarga (regorafenib) demonstrated manageable safety and potential antitumor activity for hepatitis B virus (HBV)-related metastatic HCC patients who have been previously treated with systemic therapy.

Key opinion leaders (KOLs) interviewed by GlobalData noted that CAR-T cells or adoptive cellular therapy is an emerging area that may change HCC treatment practice in the future.

Mandana Emamzadeh, PhD, Pharma Analyst at GlobalData, comments: “The majority of late-stage pipeline drugs for advanced HCC are for use in the first-line setting, which has the highest number of treated cases. Therefore, subsequent lines of therapy are being overlooked by drug developers, despite high unmet need. However, CARsgen Therapeutics conducted the study of its CAR-T cell therapy on patients who progressed on two or more lines of systemic therapy, having tried at least one TKI combined with anti-programmed death-1 (PD-1)/ programmed death ligand 1 (PD-L1) immunotherapy or FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy.”

A similar strategy of focusing on subsequent lines of therapy was used by other companies studying adoptive cellular therapy for HCC in the early-stage development including Immunotech Biopharm, Immunicum AB, Eureka Therapeutics, Adaptimmune Therapeutics, Fate Therapeutics, and Origincell Therapeutics. Therefore, investigation of heavily pretreated advanced HCC patients seems to be a general trend with CAR-T cell developers in HCC.

Emamzadeh adds: “The HCC clinical pipeline is crowded with me-too drugs targeting patients in the first-line setting. CARsgen’s CAR-GPC3 T cell therapy is a first-in-class targeted drug addressing advanced HCC patients who have progressed on or developed resistance to previous therapy—a patient population with little to no treatment options. GlobalData expects that if successful in later stage trials, CARsgen’s therapy will be beneficial to underserved patients in late-stage advanced HCC.”