Abbisko Therapeutics Obtained Approval from U.S. FDA to Conduct First-in-Human (FIH) Clinical Study of A Next-Generation FGFR4 Mutant Inhibitor ABSK012

8 Nov 2023, Shanghai—Abbisko Therapeutics Co., Ltd. (“Abbisko” hereafter) today announced that ABSK012, a highly selective small molecule inhibitor overcoming resistant mutations of fibroblast growth factor receptor 4 (FGFR4) in patients with advanced solid tumors, has obtained investigational new drug (IND) approval of the first-in-human (FIH) phase I clinical study from the U.S. FDA.

The approved study is “A Phase 1, Open-Label Study of ABSK012 to Assess Safety, Tolerability, and Pharmacokinetics in Patients with Advanced Solid Tumors”. The study population are patients with advanced solid tumors harboring specific molecular alterations, hepatocellular carcinoma (HCC) patients with FGF19 overexpression, and rhabdomyosarcoma (RMS) patients with FGFR4 mutations etc.

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 20201. Solid tumors represent more than 90% of all cancers. Liver cancer is the sixth most common cancer globally, with nearly 906,000 new cases and 830,000 deaths in 20202. In the U.S., there are more than 42,000 new cases and 31,000 deaths from liver cancer3. Notably, China accounts for approximately 50% of the incidence and mortality of liver cancer worldwide (more than 410,000 new cases and 391,000 deaths per year)4. IARC predicts that by 2040, new cases and deaths from liver cancer will further increase. Generally speaking, the treatment of liver cancer is difficult, the prognosis is poor, and the ratio of morbidity v.s. mortality is as high as 1:0.9, which seriously threatens human life and health. HCC is the main type of liver cancer, accounting for 85% to 90% of primary liver cancers5. HCC is highly malignant, about 30% of HCC has abnormal overexpression of FGF19 and poor prognosis, the existing treatment methods still cannot meet the long-term survival benefits. For the treatment of HCC, there is still a huge unmet clinical need. Sarcomas are rare and heterogeneous groups of solid tumors of mesenchymal origin accounting for only 1% of all adult malignancies6，they can be divided broadly into soft tissue sarcomas (STS) and osteosarcoma. In 2022, an estimated of 13,190 people were diagnosed with soft tissue sarcoma (STS) in the U.S., with approximately 5,130 deaths6. RMS is a subtype of STS, which is exceedingly rare in adults and accounts for 3% of all STS7.

About ABSK012

ABSK012 is a highly potent, selective, and next-generation small molecule FGFR4 inhibitor overcoming FGFR4 mutations resistant to first-generation inhibitors. The FGFR4 signaling pathway is a promising direction for the development of molecular targeted therapies in solid tumor (e.g., HCC, RMS). ABSK012 also showed anti-tumor activity and had favorable drug metabolism and pharmacokinetics properties in the preclinical study. In April 2023, ABSK012 was granted the orphan drug designation (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of soft tissue sarcoma (STS). 

Reference：

1.World Health Organisation: Globocan 2020 – All Cancers Factsheet. Available at: https://web.archive.org/web/20210707201547/https://gco.iarc.fr/today/data/factsheets/cancers/39-All-cancers-fact-sheet.pdf 

2.World Health Organisation: Globocan 2020 – Liver Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/cancers/11-Liver-fact-sheet.pdf 

3.World Health Organisation: Globocan 2020 – United States of America Factsheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/840-united-states-of-america-fact-sheets.pdf

4.World Health Organisation: Globocan 2020 – China Factsheet. Available at: http://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf

5.El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology. 2007;132(7):2557-2576. doi:10.1053/j.gastro.2007.04.061

6.National Comprehensive Cancer Network.（2023）Soft Tissue Sarcoma (version 2. 2023). 

7.Ferrari, A., Dileo, P., Casanova, M., Bertulli, R., Meazza, C., Gandola, L., Navarria, P., Collini, P., Gronchi, A., Olmi, P., Fossati-Bellani, F., & Casali, P. G. (2003). Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution. Cancer, 98(3), 571–580. https://doi.org/10.1002/cncr.11550