September 15, 2024, Abbisko Therapeutics (HKEX: 02256) presents updated clinical safety and efficacy results for its self-discovered small molecule FGFR4 inhibitor, irpagratinib (ABSK-011), from a Phase I clinical trial in patients with advanced hepatocellular carcinoma (aHCC) harboring FGF19 overexpression at the European Society of Oncology (ESMO) Congress 2024. Irpagratinib 220mg BID cohort demonstrated excellent efficacy in ICI and mTKI pre-treated aHCC patients with FGF19 overexpression, achieving an objective response rate (ORR) of 44.8% with a median duration of response (mDoR) of 7.4 months and median progression free survival (mPFS) of 5.5 months.

In addition, the design of the phase II study of pimicotinib in combination with chemotherapy and with/without toripalimab as first-line treatment for advanced pancreatic ductal adenocarcinoma (PDAC) will be presented.

Abbisko presentations at ESMO 2024:

Poster number: 983P

Title: 

Updated Safety and Efficacy of Irpagratinib (ABSK011) in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a Phase 1 study

Study background: 

Patients with FGF19+ aHCC were treated QD or BID. Here, we report the updated results from the BID cohorts to further evaluate the efficacy and safety of ABSK-011.

Study Population: 

As of September 5, 2024, 122 patients have been enrolled, including 74 in the BID cohort with doses consisting of 160mg BID, 220mg BID, and 300mg BID. 5.4% of patients were BCLC Stage B, and 89.2% BCLC Stage C, 64.9% had a Child-Pugh (CP) Score of 5, 27% CP Score of 6, and 6.8% CP Score of 7. 64.9% of patients received multiple lines of prior therapy, 85.1% of patients had previously been treated with ICIs, and 75.7% of patients had previously been treated with both ICIs and mTKIs.

Efficacy: 

Forty pre-treated HCC patients with FGF19 overexpression were treated with irpagratinib 220 mg BID. Among the 38 evaluable patients, the response rate was 36.8% (14/38), and the disease control rate (DCR) was 78.9% (30/38). The response rate from the subset of patients who had previously received ICI and mTKI therapy was 44.8% (13/29). The longest observed DoR was 16.4 months and the mDoR was 7.4 months. DCR was 79.3% (23/29). mPFS was 5.5 months.

Safety: 

One dose-limiting toxicity (DLT) was observed in the 300 mg BID cohort. The most common treatment-related adverse effects (TRAEs, >20%) were ALT elevation, diarrhea, AST elevation, hyperphosphatemia, bilirubin elevation, alkaline phosphatase elevation, platelet decrease, and total bile acid elevation. Grade 3-4 treatment-related adverse events (>5%) included AST elevation, ALT elevation, and diarrhea. No grade 5 adverse events occurred.

Conclusion: 

Currently, there is no approved standard of care for HCC patients who have progressed from first-line ICI-based therapies. The FGF19/FGFR4 signaling axis could be a novel therapeutic target for HCC. ABSK-011, a potent FGFR4 inhibitor, demonstrated a tolerable safety profile and promising anti-tumor activity as a single agent. Notably, the irpagratinib 220mg BID regimen exhibited a 44.8% ORR, 7.4 months mDoR and 5.5 months mPFS in heavily pre-treated HCC patients who had received both ICI and mTKI therapy, supporting further late-stage development of irpagratinib in such populations with substantial unmet medical need.

Poster number：1533TiP

Title: A Multicenter, Open-Label Phase II Study To Evaluate The Efficacy And Safety Of Pimicotinib (ABSK021) In Combination With Chemotherapy With Or Without Toripalimab In Patients With Advanced Pancreatic Ductal Adenocarcinoma.”