Abbisko Therapeutics announced today that updated results from their Phase 2 study evaluating irpagratinib (ABSK011) in combination with atezolizumab for advanced hepatocellular carcinoma (HCC) will be presented at the upcoming 2025 ESMO GI Congress in Barcelona, Spain, scheduled for July 2-5.
The oral presentation will showcase the combination's favorable safety profile and promising anti-tumor activity in both treatment-naive patients and those previously treated with immune checkpoint inhibitors who have FGF19-overexpressing HCC. According to the company, the data demonstrates significant objective response rate (ORR) and progression-free survival (PFS) benefits, highlighting the potential of irpagratinib-based combinations in liver cancer treatment.
Dr. Qi Cheng will deliver the presentation titled "Irpagratinib (ABSK-011) plus Atezolizumab in First-line (1L) and Immune Checkpoint Inhibitors (ICIs) Treated Advanced Hepatocellular Carcinoma (HCC) with FGF19 Overexpression (+): Updated Results of the Phase 2 ABSK-011-201 Study" on July 2, 2025.
Novel Mechanism of Action Targets Specific HCC Subtype
Irpagratinib represents a novel approach to HCC treatment as a highly-selective FGFR4 small molecule inhibitor specifically designed to target overexpression of the FGF19 signaling pathway. Epidemiological studies have established that approximately 30% of HCC patients worldwide exhibit FGF19 overexpression, creating a significant subpopulation that could benefit from targeted therapy.
The development of FGFR4 inhibitors marks an innovative strategy in HCC treatment, where therapeutic options have historically been limited. Currently, no FGFR4 inhibitor has received regulatory approval globally, positioning irpagratinib as a potential first-in-class therapy for this indication.
According to market research firm Frost & Sullivan, irpagratinib is expected to become the first breakthrough treatment specifically for advanced HCC patients with FGF19 overexpression, addressing a significant unmet medical need in liver cancer management.
Promising Clinical Data
The combination therapy builds on encouraging results previously presented at the 2024 ESMO GI Congress, where Abbisko reported that 220mg irpagratinib BID (twice daily) administered with atezolizumab achieved a 50% objective response rate in FGF19-positive HCC patients who had previously received immune checkpoint inhibition therapy.
This response rate is particularly noteworthy in the context of HCC, which has historically shown limited responsiveness to systemic therapies. The updated results to be presented this year are expected to provide further insights into the durability of these responses and additional efficacy metrics.
Strategic Collaboration with Roche
Abbisko's development strategy includes exploring irpagratinib both as monotherapy and in combination with atezolizumab, an anti-PD-L1 antibody manufactured by F. Hoffmann-La Roche and Roche (China). This combination approach leverages complementary mechanisms of action—targeted inhibition of the FGF19/FGFR4 pathway alongside immune checkpoint inhibition—potentially offering enhanced efficacy compared to either approach alone.
The collaboration represents a significant development in the HCC treatment landscape, where combination approaches are increasingly being explored to overcome the complex biology and heterogeneity of liver cancer.
Implications for HCC Treatment
Hepatocellular carcinoma remains one of the most challenging malignancies globally, with limited treatment options and poor prognosis for advanced disease. The development of targeted therapies like irpagratinib addresses the growing recognition that HCC comprises distinct molecular subtypes that may respond differently to various therapeutic approaches.
The biomarker-driven approach—focusing specifically on FGF19-overexpressing tumors—aligns with the broader trend toward precision medicine in oncology, where treatments are increasingly tailored to specific molecular characteristics of a patient's tumor.
If successful in later-stage clinical development, the irpagratinib-atezolizumab combination could represent a significant advancement for the approximately 30% of HCC patients whose tumors overexpress FGF19, offering a more targeted and potentially more effective treatment option than currently available therapies.
The upcoming presentation at ESMO GI 2025 is anticipated to provide critical insights into the potential of this novel combination and its place in the evolving treatment landscape for advanced hepatocellular carcinoma.
