Irpagratinib

2026年3月18日，上海和誉生物医药科技有限公司（以下简称“和誉医药”，港交所代码：02256）今日宣布，其自主研发的高选择性口服小分子FGFR4抑制剂依帕戈替尼（Irpagratinib/ABSK-011）在韩国一项研究者发起的临床试验（IIT）中完成首例患者给药。该研究（IAPETUS）旨在系统评估依帕戈替尼联合阿替利珠单抗及贝伐珠单抗（T+A）一线治疗FGF19过表达的晚期或不可切除肝细胞癌（HCC）患者的安全性、耐受性及疗效。这是在联合特瑞普利单抗及贝伐珠单抗生物类似物开展的II期研究以外，依帕戈替尼在晚期HCC一线治疗领域的又一项新探索。 原发性肝癌是全球第三大肿瘤相关死亡原因，其中HCC约占75%–85%。近年来，免疫联合抗血管生成治疗已成为晚期HCC的一线标准治疗选择之一。然而，临床研究与实践逐渐显示，不同分子分型患者的治疗获益存在差异。 华中科技大学同济医学院附属同济医院开展的一项回顾性研究发现，与FGF19低表达患者相比，FGF19过表达HCC患者在接受一线靶免联合治疗时的中位无进展生存期（mPFS）显著缩短（6.1个月 vs 11.4个月；p<0.05; HR=0.45, 0.22-0.89），客观缓解率（ORR）亦呈下降趋势（33.3% vs 45.2%）1。这一临床差异背后的潜在机制，可能与FGFR4/FGF19信号通路的异常激活有关。基础研究显示，该通路可通过上调肿瘤细胞程序性死亡配体-1（PD-L1）表达，促进肿瘤免疫逃逸及转移进程，从而可能削弱免疫联合治疗的疗效2,3。 值得注意的是，约30%的HCC患者存在FGF19过表达，该人群在现有标准治疗体系下仍存在未充分满足的治疗需求。因此，在标准治疗方案基础上进一步联合FGFR4抑制剂，有望从机制层面增强抗肿瘤效应，为该类患者带来额外临床获益。 依帕戈替尼是和誉医药自主研发的一款高选择性、口服小分子FGFR4抑制剂。在既往联合阿替利珠单抗治疗HCC的II期临床研究中，依帕戈替尼展现出良好的安全性、耐受性及显著的抗肿瘤活性，提示其与免疫治疗具有潜在的协同增效作用1。除IAPETUS研究以外，和誉医药近期还完成了依帕戈替尼联合特瑞普利单抗、贝伐珠单抗生物类似药的 II 期临床试验首例患者给药。未来，随着更多高质量临床研究的稳步推进，依帕戈替尼用于晚期HCC一线治疗的临床证据体系将得到进一步的完善与夯实。 在单药开发方面，依帕戈替尼同样取得积极进展。2025年5月，该药获得中国国家药品监督管理局药品审评中心（CDE）授予的突破性疗法认定（BTD），随后启动覆盖全国50余家研究中心的关键注册临床研究（文末附临床招募信息）。今年2月，和誉医药亦完成了依帕戈替尼全球多中心I期临床研究扩展阶段美国人群的首例患者给药，持续推进其全球临床开发进程。 依帕戈替尼关键注册临床患者招募 · 上下滑动查看更多信息（长按可保存长图） 参考文献 1. Cheng, Q., et al. (2025). 149MO 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. Annals of Oncology. 2. Guo C, et al. FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1. Biomed Pharmacother. 2024 Jan;170:115955. 3. Xie M, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. J Hepatol. 2023 Jul;79(1):109-125. 关于依帕戈替尼（Irpagratinib/ABSK-011） 依帕戈替尼（ABSK-011）是一种高选择性小分子FGFR4抑制剂，被开发用于治疗FGF19过表达的晚期肝细胞癌（aHCC）。研究表明，全球约30%的HCC患者存在FGF19过表达。开发针对该信号通路的靶向疗法代表了治疗HCC的一种新颖的创新方法。 当前，全球尚无FGFR4抑制剂获批上市，根据弗若斯特沙利文的分析，依帕戈替尼凭借其在竞争格局中的领先地位，有望成为首个治疗FGF19过表达HCC患者的突破性药物。 除单药之外，和誉医药同时在探索联合抗PD-L1抗体阿替利珠单抗（由F. Hoffmann-La Roche Ltd.及罗氏（中国）投资有限公司制造）的II期试验。在2025年ESMO-GI大会上，和誉医药发布了联合用药治疗aHCC患者的最新临床试验数据，其中，依帕戈替尼联用阿替利珠单抗队列在初治及既往接受过ICI治疗的FGF19过表达HCC患者中，客观缓解率（ORR）均超过50%，中位无进展生存期（mPFS）超过7个月。 Abbisko Therapeutics Announces First Patient Dosed in Clinical Study of Irpagratinib Plus T+A as First-Line Treatment for Advanced HCC 18 March 2026, Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter, HKEX code: 02256) today announced that the first patient has been dosed in an investigator-initiated trial (IIT) in South Korea evaluating its independently developed, highly selective, oral small-molecule FGFR4 inhibitor irpagratinib (ABSK-011). The study (IAPETUS) is designed to systematically evaluate the safety, tolerability, and efficacy of irpagratinib in combination with atezolizumab and bevacizumab (T+A) as a first-line treatment for patients with FGF19-overexpressing advanced or unresectable hepatocellular carcinoma (HCC). This represents a new exploration of ipagratinib in the first-line treatment of advanced HCC, in addition to the Phase II study evaluating its combination with toripalimab and bevacizumab biosimilar. Primary liver cancer ranks as the third leading cause of cancer-related mortality worldwide, with HCC accounting for approximately 75%–85% of cases. In recent years, the combination of immunotherapy and anti-angiogenic therapy has become one of the standard first-line treatments for advanced HCC. However, increasing evidence suggests heterogeneous treatment responses across molecular subtypes. A retrospective study conducted by Tongji Hospital, HUST demonstrated that, compared with patients with low FGF19 expression, those with FGF19 overexpression experienced a significantly shorter median progression-free survival (mPFS) when receiving first-line targeted immunotherapy combinations (6.1 months vs. 11.4 months; p<0.05; HR=0.45, 0.22–0.89) 1. A downward trend in objective response rate (ORR) was also observed (33.3% vs. 45.2%) 1. The underlying mechanism may be associated with aberrant activation of the FGFR4/FGF19 signaling pathway. Preclinical studies indicate that activation of this pathway can upregulate PD-L1 expression in tumor cells, thereby promoting immune evasion and metastasis, and potentially attenuating the efficacy of immunotherapy-based combinations 2,3. Notably, approximately 30% of HCC patients exhibit FGF19 overexpression, representing a population with significant unmet medical needs under the current standard-of-care paradigm. Therefore, integrating FGFR4 inhibitor into existing standard treatment regimens may mechanistically enhance antitumor activity and provide additional clinical benefits for this patient population. Irpagratinib is a highly selective, orally administered small-molecule FGFR4 inhibitor independently developed by Abbisko Therapeutics. In a previous Phase II study evaluating irpagratinib in combination with atezolizumab for HCC, the combination demonstrated favorable safety and tolerability along with antitumor activity, suggesting potential synergistic effects with immunotherapy. In addition to the IAPETUS study, Abbisko Therapeutics recently completed dosing of the first patient in a Phase II clinical trial evaluating irpagratinib in combination with toripalimab and bevacizumab biosimilar. Looking ahead, as more high-quality clinical studies continue to advance steadily, the evidence supporting irpagratinib as a first-line treatment for advanced HCC is expected to be further strengthened and expanded. In parallel with combination development, irpagratinib has also achieved significant progress as a monotherapy. In May 2025, the drug was granted Breakthrough Therapy Designation (BTD) by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA), followed by the initiation of a pivotal registrational clinical study across more than 50 research centers nationwide. In February of this year, Abbisko Therapeutics also completed dosing of the first U.S. patient in the expansion phase of the global multicenter Phase I study of irpagratinib, further advancing its global clinical development program. References 1. Cheng, Q., et al. (2025). 149MO 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. Annals of Oncology. 2. Guo C, et al. FGF19/FGFR4 signaling contributes to hepatocellular carcinoma survival and immune escape by regulating IGF2BP1-mediated expression of PD-L1. Biomed Pharmacother. 2024 Jan;170:115955. 3. Xie M, et al. FGF19/FGFR4-mediated elevation of ETV4 facilitates hepatocellular carcinoma metastasis by upregulating PD-L1 and CCL2. J Hepatol. 2023 Jul;79(1):109-125. About Irpagratinib (ABSK-011) Irpagratinib is a highly-selective FGFR4 small molecule inhibitor designed to target overexpression of the FGF19 signaling pathway. Several epidemiological studies indicate that approximately 30% of HCC patients worldwide exhibit FGF19 overexpression. Development of targeted therapies against FGFR4 represent an innovative and novel approach to the treatment of HCC. To date, no FGFR4 inhibitor has been granted regulatory approval globally. According to Frost & Sullivan, irpagratinib is expected to become the first breakthrough treatment for the treatment of HCC patients with FGF19 overexpression. In addition to monotherapy, Abbisko Therapeutics is exploring irpagratinib in combination with atezolizumab, an anti-PD-L1 antibody manufactured by F. Hoffmann-La Roche and Roche (China), in a Phase II study. At the the 2025 ESMO GI Congress, Abbisko presented clinical data showing that the combination of irpagratinib and atezolizumab achieved an objective response rate (ORR) exceeding 50% and a median progression-free survival (mPFS) of more than 7 months in FGF19-overexpressing HCC patients previously treated with immune checkpoint inhibitors. About Abbisko Therapeutics Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology. Please visit www.abbisko.com for more information. 关于和誉 和誉医药（香港联交所代码：02256）成立于2016年，是一家立足中国，着眼全球的创新药研发公司。公司的创始人和管理团队拥有多年顶尖跨国药企的研发和管理经验，并参与了多个临床及上市新药的研发。和誉医药专注于肿瘤新药研发，以小分子肿瘤精准治疗和小分子肿瘤免疫治疗药物为核心，着眼病患及医药市场的需求，秉承国际新药开发的理念和标准，致力于开发新颖及高潜力药物靶点的潜在first-in-class或best-in-class创新药物，用于改善中国及全球病人的生活质量。自成立以来，和誉医药已经建立了丰富的创新产品管线，涵盖肿瘤精准治疗领域以及肿瘤免疫治疗领域。 更多信息，欢迎访问 www.abbisko.com。

● 药闻快报 ▲关注药财社 聚焦医药界▲ 1 李彦宏创立的AI生物公司 传已秘密提交港股IPO 据彭博社3月16日消息，由百度创始人李彦宏与百度风投前首席执行官刘维于2020年共同创立的生物技术公司百图生科（北京）智能技术有限公司，已正式向港交所秘密提交IPO申请。 知情人士透露，百图生科目前正与中金公司、摩根士丹利及瑞银集团紧密合作，共同推进此次上市事宜，预计今年内将通过首次公开招募筹集数亿美元资金。 作为一家人工智能驱动的生命科学初创企业，百图生科致力于开发能够建模并预测生物机制的AI系统，旨在通过技术手段显著提升药物研发的效率与成功率。 此前，公司首席执行官刘维曾明确表示计划于一年半内寻求赴港上市。 随着近期香港医疗健康市场交易活跃度回升，AI制药赛道持续获得资本市场青睐。 尽管目前的募资规模与具体时间表仍存在变动可能，但此次IPO进程的实质性推进，标志着该公司正加速资本化进程，以应对生物计算领域日益激烈的国际竞争。 2 和誉医药FGFR4抑制剂联合 靶免疗法完成肝癌II期首例给药 2026年3月16日，和誉医药宣布其自主研发的高选择性口服FGFR4抑制剂依帕戈替尼，联合特瑞普利单抗与贝伐珠单抗标准靶免疗法，在治疗晚期或不可切除肝细胞癌的II期临床研究中完成首例患者给药。 肝细胞癌占原发性肝癌的75%至85%，其中约30%的患者存在FGF19过表达，该人群接受常规一线靶免治疗的中位无进展生存期仅6.1个月，远低于低表达人群。 研究表明，FGFR4/FGF19通路异常激活会诱导免疫逃逸，削弱疗效，目前尚无针对性获批药物。 此前依帕戈替尼联合阿替利珠单抗的II期数据已显示，FGF19过表达患者的客观缓解率超50%，安全性良好。 本次研究旨在通过三联方案阻断异常通路，实现靶向与免疫治疗的协同增效。 作为全球领先的FGFR4管线，依帕戈替尼有望填补临床空白，为精准肝癌治疗提供创新方案。 3 勃林格殷格翰启动Obrixtamig 全球III期临床 3月16日，美国临床试验收录网站信息显示，勃林格殷格翰（Boehringer Ingelheim）正式启动其CD3/DLL3双特异性抗体Obrixtamig的首个III期临床研究（DAREON®-Lung-1）。 作为全球第2款步入该阶段的同类药物，本研究是一项多中心、开放标签的随机临床试验，计划招募670名受试者。 试验旨在评估Obrixtamig联合标准疗法（阿替利珠单抗、卡铂及依托泊苷）对比单纯标准疗法，在一线治疗广泛期小细胞肺癌（ES-SCLC）患者中的有效性与安全性，主要终点设为总生存期。 前期I期研究数据显示，Obrixtamig表现出显著的抗肿瘤活性：其单药治疗经治患者的客观缓解率为21.3%；联合拓扑替康时客观缓解率提升至76%，中位无进展生存期达8个月；而在联合标准疗法时，客观缓解率为68%，且9个月无进展生存比例达52%。 该临床试验的启动标志着小细胞肺癌免疫联合治疗方案进入新阶段，后续产出的总生存期数据将成为该药物获批上市的关键支撑。 — END — 撰稿：柏佳 | 编辑：Leon | 校对：木子 | 审核：金良 投稿与开白联系：13921180988 约稿与商务合作：13951680222 声明：本文数据及信息均来自公开信息，包括不限于上市公司公告、各省证监局官网、交易所官网，各大新闻媒体网站等，数据或信息如有遗漏，欢迎更正，并以公司最终披露为准。本文不构成任何的投资建议。