Utilizing Tislelizumab to Treat Unresectable Hepatocellular Carcinoma

Ghasson K. Abou-Alfa, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center, discusses that phase 2 study of tislelizumab (BGB-A317) as treatment of patients with unresectable hepatocellular carcinoma (HCC).

The study assessed the primary end point of objective response rate in 249 patients with HCC. The treatment induced durable responses in these patients and was well-tolerated. Further exploration of the treatment strategy is underway in a phase 3 randomized study of tislelizumab versus the current standard of care therapy, sorafenib (Nexavar).

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0:08 | In brief, we're quite excited that tislelizumab is another anti PD-1, but with a very important specificity in regard to it mechanism of action have been evaluated in this phase 2 study and lead to the finding of important results, among which an increase response rate of close to about 30%, and importantly, 2 complete responses and 29 partial responses. If anything, this translated into improvement in outcome over a medium follow- up close to 9 to 10 months. Median overall survival was 12.4 months and medium progression free survival was 2.7 months with importance to re-note that the 1-year overall survival was close to 52%. Know that this is very encouraging, especially that the therapy was tolerable. And of course, we look forward for the results of the ongoing growth of a specific drug evaluating business compared to the standard, so after first-line therapy for patient with advanced, unresectable HCC.

1:26 | Tislelizumab has certain particularities, and it really does. If anything, yes, it's an anti PD-1, but intriguingly, it has a very high affinity and specificity to PD-1, which is engineered because of the minimization of the binding of the FC gamma receptor on macrophages to limit the antibody dependent phagocytosis. So, as we all know, the PD-1 is sitting like a chair, where the T cells will come in and they are invited to sit on and that's why they don't attack the cell membrane of the cancer cell. And oral anti PD-1 does escape this chair also the new cell can fall into play. Interestingly, however, with the FC gamma, this might become a little bit a more laborious process. And if anything, the tie in of the binding of the FC gamma to the macrophages, which means the T cells are bound to the macrophage will prevent that interaction from happening as powerful as can be. With this extra acid that tislelizumab provides by minimizing the binding of the FC gamma receptor to the macrophages , it rather kind of invites the direct attack of the T cells onto the tumor.