irpagratinib (ABSK011) / Abbisko - LARVOL DELTA

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 II ABSK-011-201 study (ESMO-GI 2025) - P2 | "Irpagratinib combined with Atezolizumab was safe and demonstrated promising anti-tumor activity in both 1L and ICI-treated FGF19+ HCC. The remarkable response rate along with an evident PFS benefit underscores the potential of FGFR4i-based combinations for further development in both ICI-treated and treatment-naïve settings."

Checkpoint inhibition • Clinical • IO biomarker • Metastases • P2 data • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19 • FGFR4

FGF/FGFR signaling in hepatocellular carcinoma: From molecular mechanisms to biomarker-guided therapy. (PubMed, Cancer Treat Res Commun) - "Early clinical data with irpagratinib support the rationale for combining FGFR4 inhibition with immune checkpoint blockade, but definitive validation and reproducible biomarker assays are still needed. Future translation should prioritize prospectively validated biomarker panels, mechanism-based combinations, longitudinal resistance monitoring, and models that recapitulate the cirrhotic, immune-active liver microenvironment."

Biomarker • Journal • Review • Fibrosis • Hepatocellular Cancer • Immunology • Liver Cancer • Oncology • Solid Tumor • FGF19 • FGF2 • FGF8 • FGFR3 • FGFR4

Updated safety and efficacy of ABSK-011 in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a phase I study (ESMO 2024) - P1 | "ABSK-011 demonstrated a manageable safety profile and promising anti-tumor activity as a single agent. These findings support further development of ABSK-011 at 220 mg BID in FGF19+ aHCC with prior ICI treatments."

Clinical • Metastases • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19 • FGFR4

A Study to Evaluate the Effects of Low-Fat Meal, High-Fat Meal and Omeprazole Enteric-Coated Tablets on the Pharmacokinetics of ABSK-011 Capsules in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Evaluate the Effects of Low-Fat Meal, High-Fat Meal and Omeprazole Enteric-Coated Tablets on the Pharmacokinetics of ABSK-011 Capsules in Healthy Participants (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: Abbisko Therapeutics Co, Ltd

New P1 trial

Abbisko Therapeutics Presents a Novel Joint Modeling Framework for ABSK-011 (irpagratinib) in HCC patients at the PAGE Meeting (HKEXnews) - "At this PAGE Meeting, Abbisko Therapeutics showcased two model-based drug development advances, highlighting the company’s growing expertise in quantitative pharmacology and innovative modeling methodologies. Notably, the joint TGD-PFS modeling framework for ABSK011 represents a significant contribution to the field, offering a more robust approach to support clinical decisions and pivotal trial design. Additionally, the comparative study of Maspectra and NONMEM demonstrates Abbisko Therapeutics’ proactive engagement in the practical application of a domestically developed modeling software from China, reflecting the company’s commitment to supporting homegrown technologies. These efforts underscore Abbisko’s dedication to both advancing its pipelines and contributing to the evolution of model-based drug development paradigms."

Clinical • Hepatocellular Cancer

The FOCUS19 study: Efficacy of an oral PD-L1 inhibitor combined with an oral FGF19 in advanced hepatocellular carcinoma after 1st+ line treatment (IMMUNOLOGY 2026) - "The combination of ABSK-011 and ABSK043 showed good safety and tolerability, as well as good disease control, in patients with unresectable or metastatic hepatocellular carcinoma who have FGF19 overexpression and have previously received systemic treatment."

Clinical • IO biomarker • Metastases • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19 • FGFR4

Selective FGFR4 inhibitor Irpagratinib (ABSK011) exhibits broad synergistic and combinatory anti-tumor effects with other therapeutic agents in preclinical HCC models (AACR 2024) - "The tested agents, including lenvatinib, atezolizumab plus bevacizumab, anti-PD-(L)1, SHP2 inhibitors and EGFR antagonists, were assessed across a range of preclinical models, such as cell-derived or patient-derived xenografts, engineered syngeneic models and humanized models. Synergistic anti-tumor effects of irpagratinib were observed in combination with the indicated agents, demonstrating more profound effects than either single agent alone in the selected preclinical in vivo models. In summary, these findings collectively illustrate very broad synergistic anti-tumor effects of irpagratinib when combined with various other therapeutic agents. These results may pave the road for potential novel combinatory therapeutic strategies that could expand the utility of irpagratinib and provide innovative and more effective therapies to HCC patients."

Preclinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • EGFR • FGF19 • FGFR4

Abbisko Therapeutics' FGFR4 Inhibitor Irpagratinib Granted Orphan Drug Designation by EMA for Hepatocellular Carcinoma (PRNewswire) - "In prior clinical studies, irpagratinib has demonstrated favorable safety and tolerability along with antitumor activity both as a monotherapy and in combination regimens in patients with FGF19-overexpressing advanced HCC....The pivotal registrational study of irpagratinib monotherapy administered the first patient dose in June 2025 and currently involves more than 50 clinical research centers across China, and is progressing smoothly."

Orphan drug • Hepatocellular Cancer

IAPETUS: A Prospective Study to Evaluate the Safety and Efficacy of the Combination Therapy of Irpagratinib, Atezolizumab, and Bevacizumab in Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=33 | Recruiting | Sponsor: Asan Medical Center | Not yet recruiting ➔ Recruiting | Initiation date: Nov 2025 ➔ Mar 2026

Enrollment open • Trial initiation date • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19

Abbisko Therapeutics…announced that the first patient has been dosed in a Phase II study evaluating…irpagratinib (ABSK-011), in combination with standard of care (toripalimab plus bevacizumab biosimilar) as first-line treatment for patients with advanced or unresectable hepatocellular carcinoma ('HCC') (HKEXnews)

Trial status • Hepatocellular Cancer

ABSK-011-201: A Phase 2, Open-Label Study of ABSK-011 Combined Atezolizumab or SOC in HCC Patients (clinicaltrials.gov) - P2 | N=118 | Enrolling by invitation | Sponsor: Abbisko Therapeutics Co, Ltd | Recruiting ➔ Enrolling by invitation | N=62 ➔ 118 | Trial completion date: Oct 2024 ➔ Dec 2029 | Trial primary completion date: Jul 2024 ➔ Dec 2028

Enrollment change • Enrollment status • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19

Abbisko Therapeutics…announced that the first patient in the United States has been successfully dosed in the expansion part of the global, multicenter Phase I clinical study (ABSK-011-101) of its independently developed, highly selective small-molecule FGFR4 inhibitor irpagratinib (ABSK-011) for patients with FGF19 overexpression advanced hepatocellular carcinoma (HCC) (Abbisko Therap Press Release) - "ABSK-011-101 is an open-label, global, multicenter Phase I study (NCT04906434) designed to assess the safety, tolerability, and pharmacokinetics of irpagratinib in patients with advanced solid tumors. The study consists of dose-escalation and dose-expansion parts. In the U.S., patients will be treated at the recommended dose determined from the completed dose-escalation part to further assess safety, tolerability, and preliminary efficacy in FGF19 overexpression advanced HCC."

Trial status • Hepatocellular Cancer

Abbisko Therapeutics' FGFR4 Inhibitor Irpagratinib Granted FDA Fast Track Designation for Advanced HCC Patients with FGF19 Overexpression Previously Treated with ICIs and mTKIs Therapies (Abbisko Therap Press Release) - "The FDA's Fast Track Designation was primarily based on positive results from a Phase I clinical study presented at the 2024 European Society for Medical Oncology (ESMO) Annual Congress."

Fast track • Hepatocellular Cancer

ABSK-011+BSC vs. Placebo+BSC in Previously Treated Advanced HCC With FGF19 Overexpression (clinicaltrials.gov) - P2 | N=141 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19

A Clinical Trial to Evaluate the Relative Bioavailability of New and Old ABSK-011 Capsules (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Abbisko Therapeutics Co, Ltd | Recruiting ➔ Completed | N=73 ➔ 40 | Trial completion date: Dec 2024 ➔ Sep 2025 | Trial primary completion date: Dec 2024 ➔ Sep 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date

Fibroblast growth factor 19-fibroblast growth factor receptor 4 axis: From oncogenesis to targeted-immunotherapy in advanced hepatocellular carcinoma. (PubMed, World J Gastrointest Oncol) - "Phase I clinical trials of Irpagratinib (ABSK-011) demonstrated an objective response rate of 43.5%, which increased to 55.6% combined with atezolizumab. It also firstly synthesizes combination strategies and underlying mechanisms between FGFR4 inhibitors and targeted-immunotherapy, addressing critical gaps in existing reviews. Additionally, we discuss the potential of FGF19 as a predictive biomarker, integrating mechanistic and clinical evidence to advance precision HCC therapeutics."

IO biomarker • Journal • Review • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19 • FGFR4 • PD-L1

ABSK-011-101: A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1 | N=200 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd | N=50 ➔ 200 | Trial completion date: Aug 2025 ➔ Dec 2028 | Trial primary completion date: Dec 2023 ➔ Dec 2027

Enrollment change • Trial completion date • Trial primary completion date • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor • FGF19

Irpagratinib/Atezolizumab Active in FGF19+ Advanced HCC (Oncology Nursing News) - P2 | N=62 | NCT05441475 | Sponsor: Abbisko Therapeutics Co, Ltd | "The combination of irpagratinib (ABSK011) and atezolizumab (Tecentriq) led to deep, durable responses in patients with advanced hepatocellular carcinoma (HCC) and FGF19 overexpression...according to phase 2 data presented at the 2025 ESMO GI Congress. At a median follow-up of 7.1 months, among response-evaluable patients in the treatment-naive population (n = 12/15), the overall response rate (ORR) was 50.0%; best responses included partial response (PR; n = 6), stable disease (SD; n = 5), and progressive disease (PD; n = 1). The confirmed ORR was 33.3%. The median duration of response (DOR) was not reached (NR), the disease control rate (DCR) was 91.7%, and the median progression-free survival (PFS) was 7.0 months (95% CI, 2.8-not evaluable [NE]). Among response-evaluable patients in the pretreated population (n = 17/18), the ORR was 52.9%; best responses included PR (n = 9), SD (n = 2), and PD (n = 5)."

P2 data • Hepatocellular Cancer

ABBISKO THERAPEUTICS TO PRESENT UPDATED RESULTS FROM THE PHASE 2 STUDY OF IRPAGRATINIB IN COMBINATION WITH ATEZOLIZUMAB FOR THE TREATMENT OF ADVANCED HCC AT THE 2025 ESMO GI CONGRESS (HKEXnews) - P2 | N=62 | NCT05441475 | Sponsor: Abbisko Therapeutics Co, Ltd | "...Abbisko Therapeutics...announced that updated results from the phase 2 study of irpagratinib (ABSK-011) in combination with atezolizumab for the treatment of patients with advanced hepatocellular carcinoma ('HCC') will be presented at the 2025 European Society for Medical Oncology Gastrointestinal Cancers Congress ('2025 ESMO GI Congress'....The oral presentation will highlight the safety and efficacy of irpagratinib in combination with atezolizumab in both treatment-naive and previously treated FGF19+ HCC patients. The treatment combination with irpagratinib showcases an objective response rate of ≥50% and a median progression-free survival of ≥7 months. These results further demonstrate the clinical benefit of irpagratinib in both previously treated and treatment-naive settings, offering renewed hope for patients with advanced HCC."

P2 data • Hepatocellular Cancer

Abbisko Therapeutics Completes First Patient Dosing in Registrational Study of Irpagratinib for HCC (PRNewswire) - "Abbisko Therapeutics...announced that it has completed first patient dosing in a registrational study of irpagratinib...for the treatment of Hepatocellular Carcinoma (HCC)....The registrational study of irpagratinib (ABSK-011-205) is a multi-center, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of irpagratinib in combination with Best Supportive Care (BSC) versus placebo in combination with BSC, in patients with advanced or unresectable HCC who exhibit FGF19 overexpression and have previously been treated with ICIs and mTKIs. Eligible patients will be randomized in a 2:1 ratio to receive irpagratinib or placebo."

Trial status • Hepatocellular Cancer

IAPETUS: A Prospective Study to Evaluate the Safety and Efficacy of the Combination Therapy of Irpagratinib, Atezolizumab, and Bevacizumab in Patients With Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=33 | Not yet recruiting | Sponsor: Asan Medical Center

New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Abbisko Therapeutics Receives CDE Approval of Breakthrough Therapy Designation for Irpagratinib (ABSK011) in the Treatment of HCC (PRNewswire) - "Abbisko Therapeutics...announced that its self-developed, highly selective small molecule FGFR4 inhibitor, irpagratinib (ABSK011), has received approval of Breakthrough Therapy Designation from the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) for the treatment of Hepatocellular Carcinoma (HCC). Irpagratinib is the first therapeutic agent to leverage molecularly defined biomarkers for precision-targeted treatment in patients with HCC....The approval of irpagratinib for Breakthrough Therapy Designation is based on its promising Phase I clinical trial data."

Breakthrough therapy • Hepatocellular Cancer

FOCUS-19: FGF19 Overexpression Combination Unified Study in HCC-19 (clinicaltrials.gov) - P2 | N=42 | Recruiting | Sponsor: RenJi Hospital

IO biomarker • New P2 trial • Hepatocellular Cancer • Oncology • Solid Tumor

Abbisko Therapeutics to Present Updated Results from the Phase 2 Study of Irpagratinib in Combination with Atezolizumab for the Treatment of Advanced Hepatocellular Carcinoma at the 2025 ESMO GI Congress (PRNewswire) - "Abbisko Therapeutics Co., Ltd...today announced that updated results from the phase 2 study of irpagratinib (ABSK011) in combination with atezolizumab for the treatment of advanced hepatocellular carcinoma (HCC) will be presented at the 2025 ESMO GI Congress, taking place in Barcelona, Spain from July 2 to July 5. The oral presentation will highlight the regimen's favorable safety and promising anti-tumor activity in both treatment-naive and previously treated FGF19+ HCC patients. The evident objective response rate (ORR) and progression free survival (PFS) benefit underscores the potential of irpagratinib-based combinations in the treatment of HCC."

P2 data • Hepatocellular Cancer