irpagratinib (ABSK011) / Abbisko - LARVOL DELTA

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

Irpagratinib (ABSK-011) plus Atezolizumab in Frist-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 (ESMO-GI 2025) - No abstract available

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

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

A Mass Balance Study of [14C]ABSK011 (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: Abbisko Therapeutics Co, Ltd

New P1 trial

Hong Kong Stocks Move | Heyu-B (02256) rose nearly 4% and was approved by the CDE to conduct a registration clinical study of irpagratinib in the treatment of hepatocellular carcinoma [Google translation] (Sina Corp) - "...Heyu Pharmaceuticals recently announced that its independently developed highly selective small molecule FGFR4 inhibitor irpagratinib (ABSK011) has been approved by the Center for Drug Evaluation (CDE) of the China National Drug Administration to conduct a registration clinical study for the treatment of hepatocellular carcinoma (HCC). This study will serve as a key basis to support the launch of irpagratinib, and also marks an important step for irpagratinib in the treatment of advanced or unresectable hepatocellular carcinoma (HCC)."

New trial • Hepatocellular Cancer

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

Heyu-B (02256.HK) subsidiary released the latest clinical progress of irpagratinib and pimicotinib at the ESMO Annual Meeting [Google translation] (Sina Corp) - P1 | N=50 | NCT04906434 | Sponsor: Abbisko Therapeutics Co, Ltd | "Heyu-B...announced that it will announce the latest clinical data on the safety and efficacy of its independently developed small molecule FGFR4 inhibitor irpagratinib (ABSK011) in a Phase I clinical trial for advanced hepatocellular carcinoma...at the 2024 European Society of Oncology Annual Meeting...The data released this time showed that the 220mg irpagratinib twice daily ('BID') group showed excellent efficacy in FGF19 overexpressing aHCC patients treated with immune checkpoint inhibitors ('ICIs') and multi-target small molecule tyrosine kinase inhibitors ('mTKIs'), with an overall response rate ('ORR') of 44.8%....In addition, the design of a Phase II clinical study of the small molecule CSF-1R inhibitor pimicotinib (ABSK021) combined with chemotherapy with or without toripalimab as a first-line treatment for advanced pancreatic ductal adenocarcinoma (PDAC) will also be made public at this conference."

Clinical protocol • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor

Hong Kong Stock Market Movement | Heyu-B (02256) rose more than 5% and is expected to make more than 200 million yuan in profit in the first half of the year, turning losses into profits year-on-year [Google translation] (Sina Corp) - "On the news front, Heyu will release its 2024 interim results on August 12. The company previously issued a profit warning, expecting total revenue in the first half of the year to be approximately RMB 497 million, a significant year-on-year increase; profit of RMB 200 million to RMB 220 million, a year-on-year turnaround. In addition to improving cost control by improving business operating efficiency, it also benefited from the out-licensing agreement for pimicotinib (ABSK021) and the first payment of US$70 million (RMB 497 million) with Merck....In addition, the company will announce the latest clinical data on the safety and efficacy of its independently developed highly selective small molecule FGFR4 inhibitor Irpagratinib in a Phase I clinical trial for advanced hepatocellular carcinoma with overexpression of FGF19 at the European Society of Oncology (ESMO) Annual Meeting in 2024."

Commercial • P1 data • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

50% ORR: Impressive Clinical Trial Data for Irpagratinib Combined with Atezolizumab in Advanced Hepatocellular Carcinoma Stuns ESMO-GI Congress (PRNewswire) - P2 | N=62 | NCT05441475 | Sponsor: Abbisko Therapeutics Co, Ltd | "Abbisko Therapeutics Co., Ltd...announced that it has presented new phase II clinical data of its highly selective FGFR4 inhibitor irpagratinib (ABSK011) in combination with atezolizumab for the treatment of advanced hepatocellular carcinoma (HCC) at the 2024 ESMO-GI Congress. The presentation highlights that 220mg BID of irpagratinib in combination with atezolizumab demonstrated promising antitumor activity with an objective response rate (ORR) of 50% in FGF19+ HCC patients....Given the encouraging preliminary results from this study, Abbisko plans to explore dual/triple combinations with irpagratinib in earlier lines of therapy for HCC."

P2 data • Trial status • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

A phase II study of ABSK-011 plus atezolizumab in patients with advanced hepatocellular carcinoma (HCC) (ESMO-GI 2024) - P2 | "ABSK-011 in combination with atezolizumab showed encouraging anti-tumor activity and manageable safety profile which supports further development of the regimen in FGF19+ HCC and exploration of ABSK-011 based double/triple combinations in earlier lines."

Clinical • IO biomarker • Metastases • P2 data • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • FGF19

Improvements in advanced hepatocellular carcinoma to repeat implementation of primary protocol after cancer progression occurs following sequential systemic therapy and a clinical trial: A case report. (PubMed, Medicine (Baltimore)) - "The combined treatment of TACE plus systemic therapy might be an appropriate subsequent treatment."

Journal • Metastases • Fatigue • Gastrointestinal Cancer • Hepatitis B • Hepatocellular Cancer • Hepatology • Infectious Disease • Oncology • Solid Tumor • AFP • 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

A Clinical Trial to Evaluate the Relative Bioavailability of New and Old ABSK-011 Capsules (clinicaltrials.gov) - P1 | N=73 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd

New P1 trial

First-in-human study of ABSK-011, a novel, highly selective fibroblast growth factor receptor (FGFR) 4 inhibitor for treating advanced hepatocellular carcinoma (HCC) with FGF19 overexpression (ESMO 2023) - P1 | "Pathway inhibition was observed by increased C4, total bile acids, FGF19, and decreased total cholesterol at all dose levels. Conclusions The promising response rate and manageable safety profile from this phase I study suggest that ABSK-011 may have clinical benefit for HCC pts with prior therapies through biomarker selection of FGF19."

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

Abbisko will debut two blockbuster clinical research results at the 2023 European Society for Medical Oncology (ESMO) (PRNewswire) - P1 | N=50 | NCT04906434 | Sponsor: Abbisko Therapeutics Co, Ltd | "Abbisko Therapeutics...announced that the clinical results of first-in-human study of FGFR4 inhibitor Irpagratinib (ABSK011)...will be presented at the 2023 European Society for Medical Oncology (ESMO) annual meeting to be held in Spain, from October 20 to 24, 2023.....ABSK-011 was well-tolerated in HCC pts. BID cohorts demonstrated a promising antitumor activity with an ORR of 40.7% in FGF19+ HCC pts with prior therapies, which suggests that ABSK-011 may have clinical benefit through biomarker selection of FGF19. The study is still ongoing, and the efficacy of BID cohorts warrants further investigation."

P1 data • Hepatocellular Cancer

Heyu (02256): ABSK011 is approved to carry out clinical trials of combination drugs for hepatocellular carcinoma in the Mainland [Google translation] (Yahoo Sports) - "Heyu...announced that its independently developed highly selective small molecule fibroblast growth factor receptor 4 (FGFR4) inhibitor Irpagratinib (ABSK011) is combined with lenvatinib to treat advanced or unresectable hepatocytes. The Phase II clinical trial application (IND) for cancer (HCC) was approved by the National Medical Products Administration (NMPA) of China."

New trial • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

Inhibition of fibroblast growth factor receptor 4 (FGFR4) signaling activates tumor interferon (IFN) signaling in hepatocellular carcinoma (HCC) (SITC 2022) - "In addition, we found that ABSK011 increased CD8 + T cell infiltration in humanized HCC mouse models. Conclusions These preclinical data demonstrated that ABSK011 treatment increased IFN related response as well as CD8 + T cell infiltration in FGF19 overexpressed HCC models, supporting the combination of FGFR4 inhibitor and immune checkpoint molecules such as anti-PD-(L)1 antibodies to achieve enhanced antitumor activity."

IO biomarker • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • CD8 • CXCL10 • FGF19 • FGFR4 • IFIT1 • IRF1 • PD-L1

Combination synergy of FGFR inhibitors with other therapeutic agents in FGFR-deregulated cancer models (AACR-NCI-EORTC 2022) - "Currently three FGFR inhibitors have been approved as monotherapy to treat locally advanced or metastatic urothelial carcinoma with FGFR2/3 alterations (erdafitinib) and unresectable cholangiocarcinoma with FGFR2 fusions (pemigatinib and infigratinib) through accelerated approval process...Materials and We tested a set of small molecule inhibitors that targeting the components related to FGFR pathway, including but not limited to PI3Ki, AKTi, mTORi, SHP2i, SOS1i, MEKi, CDK4/6i and METi, in cellular combination experiments with a pan-FGFR inhibitor ABSK091 (formerly AZD4547) or a FGFR4 selective inhibitor ABSK011 for various FGFR-deregulated models, including endometrial cancer cells harboring FGFR2 mutations, gastric cancer cells with FGFR2 amplification and overexpression, bladder cancer cells bearing FGFR3 fusion and hepatocellular carcinoma (HCC) cells with FGF19 amplification and overexpression... Synergistic effects on cell growth inhibition were observed in..."

Preclinical • Biliary Cancer • Bladder Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • Urothelial Cancer • CDK4 • FGF19 • FGFR2 • FGFR3 • FGFR4

A Phase 2, Open-Label Study of ABSK-011 Combined Atezolizumab in HCC Patients (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd | Not yet recruiting ➔ Recruiting | Initiation date: Jul 2022 ➔ Dec 2021

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

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1 | N=50 | Recruiting | Sponsor: Abbisko Therapeutics Co, Ltd | Trial completion date: Jan 2023 ➔ Aug 2025 | Trial primary completion date: Oct 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • FGF19

A Phase 2, Open-Label Study of ABSK-011 Plus Atezolizumab to Assess Safety, Tolerability, Pharmacokinetics, and Anti-tumor Efficacy in Patients With Advanced or Unresectable Hepatocellular Carcinoma (clinicaltrials.gov) - P2 | N=62 | Not yet recruiting | Sponsor: Abbisko Therapeutics Co, Ltd

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

A Study to Assess the Safety, Tolerability, and Pharmacokinetics of ABSK-011 in Patients With Advanced Solid Tumor (clinicaltrials.gov) - P1; N=50; Recruiting; Sponsor: Abbisko Therapeutics Co, Ltd

Clinical • New P1 trial • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • FGF19