ESMO Asia丨和誉医药公布口服PD-L1抑制剂ABSK043联合EGFR抑制剂伏美替尼治疗NSCLC的II期临床初步结果

表皮生长因子受体（EGFR）突变是NSCLC中最常见的驱动基因突变。尽管第三代EGFR-TKIs已成为EGFR突变晚期NSCLC的一线标准治疗方案，但既往研究提示，对于EGFR突变合并PD-L1高表达的患者，第三代EGFR-TKIs的疗效劣于PD-L1低表达或阴性患者^1,2。此外，虽然免疫治疗已在多个癌种中表现出卓越疗效，但PD-1/PD-L1抗体与EGFR-TKI的联合方案因严重毒副反应而受到限制，使得该类患者人群的临床需求仍未得到满足。

在本届ESMO Asia 2025年会上，上海交通大学医学院附属上海胸科医院陆舜教授以壁报形式展示了正在开展的II期研究（ABSK043-202）剂量递增阶段的积极结果。该研究分为剂量递增和剂量扩展两部分。剂量递增阶段共纳入21例EGFR突变且PD-L1阳性的经治晚期NSCLC患者，其中17例患者曾接受过第三代EGFR-TKIs治疗。

研究结果显示，ABSK043联合伏美替尼表现出可控的安全性和良好的耐受性。截至数据分析时，未观察到剂量限制性毒性和间质性肺炎（ILD），最常见的治疗相关不良反应（TEAE）为1-2级，未观察到4级或5级TEAE。

该联用方案还展现出积极的抗肿瘤活性，依据RECIST v1.1标准评估的疾病控制率（DCR）达到71%，共有14例患者实现靶病灶缩小。5例达到部分缓解（PR）的患者中，有4例曾接受过第三代EGFR-TKI的治疗。截至数据分析时，中位缓解持续时间（DOR）尚未达到。

剂量递增阶段的研究结果表明，ABSK043联合伏美替尼不仅安全性可控、耐受性良好，还展现出令人鼓舞的初步抗肿瘤活性。这种完全口服的“靶免联合”创新治疗策略有望克服以往靶向联合免疫治疗的安全性瓶颈。上述积极结果为正在开展的剂量扩展阶段——ABSK043联合伏美替尼用于初治EGFR突变且PD-L1阳性的NSCLC患者的一线治疗研究奠定了坚实基础。

关于ABSK043

ABSK043为一款全新的具备优异活性及高度选择性的口服小分子PD-L1抑制剂。癌细胞可以利用PD-1及其配体PD-L1这些免疫检查点来逃避免疫监管和清除，抑制或限制T细胞应答。ABSK043可与PD-L1受体特异性结合并诱导其从细胞表面内吞，有效地抑制PD-1/PD-L1的相互作用，解除PD-L1介导的T细胞活化抑制作用。ABSK043在多个临床前模型中展现出与已获批PD-L1抗体相当的抗肿瘤功效。截至目前，全球已有多款PD-1/PD-L1抗体药物获批上市，但并无PD-1/PD-L1小分子药物获批。ABSK043目前正在澳大利亚和中国开展针对晚期实体肿瘤的I期临床试验。

关于伏美替尼

伏美替尼是中国原研、具有自主知识产权的第三代EGFR-TKI，分别于2021年3月、2022年6月获批EGFR突变的局部晚期或转移性NSCLC成人患者的二线、一线治疗适应症，并均已被纳入国家医保目录。目前伏美替尼针对EGFR 20外显子插入突变NSCLC患者一线治疗适应症的包括中国、美国、英国、法国、日本、韩国等多个国家在内的全球多中心III期注册临床研究正在顺利进行中。此外，伏美替尼针对EGFR 20外显子插入突变NSCLC治疗的适应症获得中、美监管机构的突破性疗法认定；针对NSCLC EGFR敏感突变辅助治疗、PACC突变NSCLC一线治疗、EGFR敏感突变NSCLC伴脑转移患者治疗、EGFR非经典突变辅助治疗的注册临床研究也在顺利推进中。

关于艾力斯

上海艾力斯医药科技股份有限公司成立于2004年3月，是一家以全球医药市场需求为导向，专注于肿瘤治疗领域，集新药研发、生产和商业化为一体的创新型制药企业。艾力斯医药以科技关爱生命为发展理念，以开发首创药物和同类最佳药物为首要目标。历经20年坚持不懈的努力，艾力斯已经成功自主研发，获批两款创新药，具备持续创制具有自主产权的疗效确切、市场最优的抗肿瘤新药之综合实力。2020年12月2日，上海艾力斯医药科技股份有限公司正式在上海证券交易所科创板挂牌上市（股票代码：688578）。

参考文献

1. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138–143.

2. Niu J, Jing X, Xu Q, et al. Strong PD-L1 affect clinical outcomes in advanced NSCLC treated with third-generation EGFR-TKIs. Future Oncol. 2024;20(32):2481-2490.

Abbisko Therapeutics Presents Preliminary Phase II Results of Oral PD-L1 Inhibitor ABSK043 Combined with EGFR Inhibitor Firmonertinib for the Treatment of NSCLC at ESMO Asia 2025

8 December 2025, Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter, HKEX code: 02256.HK) today announced preliminary results from the dose escalation phase of the ongoing Phase II clinical study (ABSK043-202) evaluating the company’s investigational oral small-molecule PD-L1 inhibitor, ABSK043, in combination with third-generation EGFR-TKI, firmonertinib from Shanghai Allist Pharmaceuticals Co., Ltd. ("Allist", SSE code: 688578.SS) for the treatment of Non-small Cell Lung Cancer (NSCLC) at the European Society for Medical Oncology Asia Congress 2025 (ESMO Asia 2025). Data showed that the combination demonstrated favorable safety and tolerability. Based on the favorable safety profile, regulatory authorities have agreed to expand the program into a first-line study in treatment-naïve patients with EGFR mutated, PD-L1 positive NSCLC.

Epidermal Growth Factor Receptor (EGFR) mutations are the most common oncogenic drivers in NSCLC. Although third-generation EGFR TKIs are the established front-line standard of care for EGFR-mutated NSCLC, studies have shown that patients with EGFR mutations and high PD-L1 expression derive less benefit from EGFR-TKIs than those with low or negative PD-L1 expression1,2. Moreover, despite the broad clinical impact of immunotherapy across multiple tumor types, combinations of PD-1/PD-L1 antibodies with EGFR-TKIs have been limited by substantial toxicities, underscoring a significant unmet need in this patient population.

At ESMO Asia 2025, Professor Shun Lu from Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, presented positive findings from the ongoing phase II study (ABSK043-202). In the dose-escalation phase, a total of 21 previously treated patients with EGFR-mutated, PD-L1-positive advanced NSCLC were enrolled, among whom 17 had received prior third-generation EGFR-TKIs.

The results showed that the combination of ABSK043 and firmonertinib was well-tolerated and had a manageable safety profile. As of the data cutoff, no Dose-limiting Toxicities (DLTs), and no Interstitial Lung Disease (ILD) were observed. The most common Treatment-emergent Adverse Events (TEAEs) were all Grade 1-2, with no Grade 4 or 5 TEAEs observed.

The combination demonstrated promising anti-tumor activity. Based on RECIST v1.1, the Disease Control Rate (DCR) reached 71% with 14 patients achieving target lesion size regression. Among the 5 patients who achieved Partial Response (PR), 4 had received a prior third-generation EGFR-TKI. As of data cutoff, median Duration of Response (DOR) was not reached.

The dose-escalation findings suggest that the combination of ABSK043 and firmonertinib demonstrates a favorable safety and tolerability profile, along with encouraging preliminary antitumor activity. This novel “targeted-plus-immuno-therapy” oral-oral treatment strategy has the potential to overcome toxicity challenges previously associated with combining EGFR-TKIs and immunotherapy antibodies. These positive results lay the groundwork for the ongoing dose-expansion phase, evaluating ABSK043 and firmonertinib as first-line treatment for treatment-naïve patients with EGFR mutated, PD-L1 positive NSCLC.

About ABSK043

ABSK043 is a novel, orally bioavailable, highly selective small molecule PD-L1 inhibitor wholly owned by Abbisko Therapeutics. Tumor cells can exploit immune checkpoints such as PD-1 and its ligand PD-L1 to evade immune detection and clearance, thereby suppressing or limiting T-cell responses. ABSK043 selectively binds to the PD-L1 receptor and induces its internalization from the cell surface, effectively inhibiting the PD-1/PD-L1 interaction and alleviating PD-L1-mediated suppression of T-cell activation. In preclinical models, ABSK043 has demonstrated anti-tumor efficacy comparable to approved PD-L1 antibodies. While several PD-1/PD-L1 monoclonal antibodies have been approved worldwide, there are currently no approved orally bioavailable PD-1/PD-L1 small molecule drugs. ABSK043 is currently being explored in an ongoing Phase I clinical trial for advanced solid tumors in Australia and China.

About Furmonertinib

Furmonertinib is a self-developed 3rd generation of EGFR-TKI with independent IP from China. It is approved by CDE for the second-line and first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR mutations in March 2021 and June 2022, respectively, both of which are included in the National Reimbursement Drug List. Thus far, the global multi-center (including China, the United States, the United Kingdom, France, Japan, South Korea, etc.), registrational Phase III clinical study of Furmonertinib is well advanced, which is used for the first-line treatment of NSCLC patients harboring EGFR Exon 20 insertion mutations. In addition, Furmonertinib has been granted as Breakthrough Therapy Designation in China and the United States for the treatment of NSCLC with EGFR Exon 20 insertion mutations. The registrational clinical studies for adjuvant treatment of NSCLC with EGFR-sensitive mutations, first-line treatment for NSCLC with PACC mutations, treatment of EGFR-sensitizing mutation NSCLC with brain metastases, and adjuvant treatment for NSCLC with uncommon EGFR mutations are also progressing smoothly.

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.

About Allist

Shanghai Allist Pharmaceuticals Co., Ltd, founded in March, 2004, is an innovative pharmaceutical company with a fully integrated system for research and development, manufacturing, and commercialization of novel oncology drugs with a purpose to meet with medical needs across the globe. On December 2nd, 2020, Shanghai Allist Pharmaceuticals Co., Ltd. was officially listed on the Science and Technology Innovation Board of the Shanghai Stock Exchange (stock number: 688578).

References

1. Brown H, Vansteenkiste J, Nakagawa K, et al. Programmed cell death ligand 1 expression in untreated EGFR mutated advanced NSCLC and response to osimertinib versus comparator in FLAURA. J Thorac Oncol. 2020;15(1):138–143.

2. Niu J, Jing X, Xu Q, et al. Strong PD-L1 affect clinical outcomes in advanced NSCLC treated with third-generation EGFR-TKIs. Future Oncol. 2024;20(32):2481-2490.

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。