15 December 2022, Shanghai – Abbisko Therapeutics Co., Ltd. (“Abbisko Therapeutics” hereafter) announced today the preliminary Phase I efficacy and safety results of its potent and highly selective small molecule inhibitor of fibroblast growth factor receptor 4 (“FGFR4”) Irpagratinib (ABSK011), in the treatment of second-line hepatocellular carcinoma (“HCC”) with fibroblast growth factor 19 (“FGF19”) overexpression.
About Phase I trial of Irpagratinib (ABSK011) (NCT04906434)
NCT04906434 is an open-label, multi-center Phase I trial of Irpagratinib (ABSK011) with an escalation part (Phase Ia) and an expansion part (Phase Ib). In the Phase Ia trial, the Company assessed multiple dosages, based on safety, tolerability, PK and PD data obtained from the Phase Ia trial, 180mg QD was identified as the first recommended dose for expansion (“RDE”) in 2021. We have extended to higher doses including but not limited to 320mg QD, 400mg QD and 160mg BID for dose escalation.
The primary objective of Phase Ib trial is to evaluate the preliminary anti-tumor activity of Irpagratinib (ABSK011) in advanced HCC patients with FGF19 overexpression. We are currently conducting the Phase Ib monotherapy trial at 180mg QD in second-line treatment of HCC patients with FGF19 overexpression and will explore higher dose or dosing schedule for expansion in addition to 180mg QD in China's mainland.
Preliminary efficacy and safety data for 42 HCC patients, out of which 27 patients are FGF19 IHC+, has been analyzed as of September 2022.
• The preliminary proof-of-concept data of Irpagratinib (ABSK011) Phase I has shown promising efficacy in FGFR19+ HCC patients, with 22% objective response rate (“ORR”) (4/18) in patients with high FGF19 expression and 33.3% ORR (2/6) in the 160mg BID cohort. Irpagratinib (ABSK011) is well tolerated across all cohorts.
• Patient group with high expression of FGF19, which was observed in 67% of the FGF19 IHC+ HCC patients, experienced 22% ORR (4/18)
• Patients in the 160mg BID cohort in dose escalation were all FGF19+ and experienced 33% ORR (2/6).
• No drug related adverse effect of grade 4 or above was reported.
• Diarrhea was reported in 72.9% of patients, which is an expected on-target toxicity related to enhanced bile-acid secretion through inhibition of FGFR4. Most patients experienced low-grade diarrhea and only one patient (2.1%) experienced grade 3 diarrhea.
• Most ALT and AST elevations were transient and manageable with supportive care, and only a small number of patients needed dose interruption or reduction.
• No ocular or nail toxicity was reported.
About Irpagratinib (ABSK011)
Irpagratinib (ABSK011) is a potent and highly selective small molecule inhibitor of FGFR4. Irpagratinib (ABSK011) is being developed for the treatment of advanced HCC with hyperactivation of FGF19/FGFR4 signaling. The FGFR4 signaling pathway is a promising direction for the development of molecularly targeted therapies in HCC. Irpagratinib (ABSK011) demonstrated improved potency and anti-tumor efficacy compared to competitors as well as favorable physical-chemical properties in preclinical studies. We believe Irpagratinib (ABSK011) is potentially a novel and leading FGFR4 inhibitor for the treatment of HCC patients with hyper-activation of FGF19/FGFR4 pathway based on competitive landscape of FGFR4 inhibitors globally, according to Frost & Sullivan.
Abbisko Therapeutics is also conducting a Phase II trial of Irpagratinib (ABSK011) in combination with the anti-PD-L1 antibody atezolizumab produced by F. Hoffmann-La Roche Ltd. and Roche China Holding Ltd. (“Roche”) in late stage HCC patients with FGF19 overexpression in China's mainland. Patient enrollment is ongoing.
In November 2022, ABSK011 was given the generic name “Irpagratinib” by World Health Organization under the International Nonproprietary Name system.
About hepatocellular carcinoma
HCC is the most common type of liver cancer, one of the most lethal cancers and the third most- common cause of cancer-related deaths worldwide. In 2020, the number of new HCC cases reached 0.8 million worldwide, and is expected to reach 1.0 million by 2030, according to Frost & Sullivan. Despite advances in the treatment of HCC, there remains a significant unmet needs for treatments of FGFR4-driven HCC. Patients with an overexpression of FGF19/FGFR4 account for approximately 30% of total HCC patients worldwide, according to Frost & Sullivan. Currently, no FGFR4 inhibitor has been approved to the market yet as far as we are aware.