口服PD-L1小分子抑制剂ABSK043联合伏美替尼治疗非小细胞肺癌的II期临床研究完成首例患者给药

研究分为剂量递增阶段和扩展阶段两部分，其中剂量递增阶段将评估不同剂量的 ABSK043 联合伏美替尼治疗 EGFR 基因突变阳性的、经治的局部晚期或转移性 NSCLC 患者的安全性和耐受性，推荐在中国患者人群中口服 ABSK043 联合伏美替尼的治疗方案，并初步评估抗肿瘤活性。扩展阶段将评估推荐剂量（一个或多个）下 ABSK043 联合伏美替尼一线治疗 EGFR基因突变阳性的局部晚期或转移性NSCLC患者的疗效，同时也将进一步评估ABSK043联合伏美替尼的安全性、耐受性以及 PK 特征。

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。截止目前，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、NSCLC EGFR罕见突变一线治疗的III期临床研究也在顺利推进中。

First Patient Dosed in Phase II Clinical Study of ABSK043, an Oral PD-L1 Small-Molecule Inhibitor, in Combination with Furmonertinib in Patients with Non-Small Cell Lung Cancer (NSCLC)

December 11, 2024, Abbisko Therapeutics Co., Ltd. (HKD: 02256) today announced that it has dosed its first patient in a phase II, open-label study to evaluate the efficacy and safety of ABSK043 in combination with furmonertinib patients with EGFR-mutated, locally advanced or metastatic NSCLC. ABSK043 is an orally bioavailable, highly selective and potent small molecule PD-L1 inhibitor independently developed by Abbisko Therapeutics and is currently being explored for the treatment of malignant neoplasms. Furmonertinib, also known as firmonertinib, is a Class I New Drug that is a novel irreversible, selective third-generation EGFR TKI independently developed by Shanghai Allist Pharmaceuticals. The combination of ABSK043 and furmonertinib is expected to improve clinical anti-tumor efficacy for patients with advanced lung cancer with EGFR mutations.

The ongoing study is divided into two parts: a dose escalation and expansion phase. The dose escalation phase will evaluate the safety and tolerability of ABSK043 in combination with furmonertinib in Chinese patients with previously treated, EGFR-mutant, locally advanced or metastatic NSCLC who are recommend a combination regimen, and will conduct a preliminary assessment of anti-tumor activity. The expansion phase will evaluate the efficacy of ABSK043 in combination with furmonertinib as a first-line treatment for patients with EGFR-mutant locally advanced or metastatic NSCLC at the one or more recommended doses, and will further assess the safety, tolerability and PK profile of the combination regimens.

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 phase III clinical studies for adjuvant treatment of NSCLC with EGFR-sensitive mutations and for the first-line treatment of NSCLC with uncommon EGFR mutations are also progressing smoothly.