ABBISKO-B (02256): The first patient in Phase II clinical trial of combined targeted immunotherapy with ipagotinib for first-line treatment of advanced liver cancer has been dosed.

ABBISKO-B (02256) announced that its subsidiary Shanghai Heyu Biomedical Technology Co., Ltd. (Heyu Medicine) has completed the first patient dosing in a Phase II clinical study for the first-line treatment of advanced or unresectable hepatocellular carcinoma (HCC) with its independently developed highly selective oral small molecule FGFR4 inhibitor Irpagratinib (ABSK-011) in combination with standard therapy (Tremelimumab + Bevacizumab biosimilar). Primary liver cancer is the third leading cause of cancer-related deaths globally, with HCC accounting for approximately 75%-85% of cases. Currently, the "targeted therapy plus immunotherapy" regimen of immune checkpoint inhibitors combined with anti-angiogenic therapy has become the first-line standard treatment for advanced HCC. However, clinical practice has shown differences in treatment outcomes for patients with different molecular subtypes. Retrospective analysis shows that compared to patients with low expression of FGF19, patients with overexpression of FGF19 have significantly shorter median progression-free survival (mPFS) after first-line targeted immunotherapy (6.1 months vs 11.4 months) and a decreasing trend in objective response rate (ORR) (33.3% vs 45.2%). This difference may be related to abnormal activation of the FGFR4/FGF19 signaling pathway. Sustained activation of this pathway can upregulate PD-L1 expression in tumor cells, thereby promoting immune escape and tumor metastasis, weakening the efficacy of immunotherapy. Therefore, combining FGFR4 inhibitors with the existing standard regimen of immunotherapy combined with anti-angiogenic therapy may enhance anti-tumor activity through complementary mechanisms and potentially provide additional clinical benefits to patients in this group. However, despite up to 30% of HCC patients having FGF19 overexpression, there is currently no approved therapy targeting this pathway, leading to unmet treatment needs in this population under existing standard treatment regimens. Irpagratinib is a highly selective, orally available small molecule FGFR4 inhibitor developed independently by Heyu Medicine, which can target the FGFR4/FGF19 signaling pathway precisely. At the 2025 European Society for Medical Oncology Congress on Gastrointestinal Cancers (ESMO GI), Heyu Medicine announced the results of a Phase II study of Irpagratinib in combination with Atezolizumab for the treatment of HCC. In patients with FGF19 overexpression who were treatment-nave or had previously received immune checkpoint inhibitor therapy, this combination therapy achieved ORR of over 50% and mPFS of over 7 months, with controllable safety and no new safety signals observed. These results highlight the potential synergistic effect of Irpagratinib when combined with immunotherapy, laying a solid foundation for further research on Irpagratinib in combination with first-line standard therapy. Based on these positive research results, Heyu Medicine has officially initiated a clinical study of Irpagratinib in combination with Tremelimumab and Bevacizumab biosimilar for the first-line treatment of advanced or unresectable HCC patients with FGF19 overexpression, aiming to systematically evaluate the safety, tolerability, and preliminary efficacy of this triple therapy. In addition to this study, researchers worldwide are actively exploring new strategies for Irpagratinib in combination with more standard therapies. With the advancement of more high-quality clinical research and accumulation of more data, Irpagratinib holds promise for bringing new hope to HCC patients with FGF19 overexpression and facilitating the development of more precise and personalized approaches to HCC diagnosis and treatment. Irpagratinib is a highly selective small molecule FGFR4 inhibitor designed to target the overexpression of the FGF19 signaling pathway. Epidemiological studies have shown that approximately 30% of HCC patients globally have FGF19 overexpression. The development of targeted therapies against FGFR4 represents an innovative and novel approach to treating HCC. In addition to monotherapy, Heyu Medicine is also exploring a Phase II trial of Irpagratinib in combination with anti-PD-L1 antibody. Clinical data presented by Heyu Medicine at the 2025 ESMO-GI Congress showed that in HCC patients with FGF19 overexpression who had previously received immune checkpoint inhibitor therapy, the combination of Irpagratinib and Atezolizumab achieved ORR of over 50% and mPFS of over 7 months.