口服PD-L1小分子抑制剂ABSK043联合FGFR2/3小分子抑制剂ABSK061治疗实体瘤的II期临床完成首例胃癌患者给药

ABSK061-201是一项评估ABSK061和ABSK043联合或不联合化疗在FGFR2/3改变的转移性/不可切除的实体瘤患者中的安全性及有效性的开放性多中心II期临床研究。试验包括剂量递增和扩展期两个部分。剂量递增将评估ABSK061+ABSK043在FGFR2/3激活改变或过表达的转移性/不可切除的晚期实体瘤患者中的安全性、耐受性、初步疗效和PK特征，并推荐用于扩展期的给药剂量。

扩展期将在多个不同的实体瘤队列，入组包含特定FGFR2/3基因改变的肿瘤类型（包括HER2阴性胃/胃食管交界癌），评估ABSK061+ABSK043联合或不联合化疗的抗肿瘤疗效。

关于ABSK061

ABSK061是和誉医药独立自主研发并拥有全球知识产权的一款新一代口服、高活性、高选择性小分子FGFR2/3抑制剂，也是全球范围内第一款进入临床的FGFR2/3选择性抑制剂。首代泛FGFR抑制剂已在针对多种携带FGFR2/3变异的肿瘤中展现出临床疗效并在全球范围内逐步获批上市，但安全窗及药效均受限于FGFR1抑制相关副作用。通过降低对FGFR1的抑制以及保持对FGFR2/3的高活性，ABSK061作为第二代FGFR抑制剂有望在临床上取得更好的安全窗及疗效。除肿瘤以外，ABSK061还具备拓展用于治疗包括软骨发育不全在内的多种非肿瘤适应症的巨大潜力。

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。

First-Patient Dosed in Gastric Cancer in Phase II Clinical Study Evaluating ABSK043, an Oral PD-L1 Inhibitor, in Combination with ABSK061, an Oral FGFR2/3 Inhibitor, for Solid Tumors

22, November 2024, Shanghai – Abbisko Therapeutics Co., Ltd. (HKD：02256) today announced that the first gastric cancer patient has been dosed in “A Phase 2， Multicenter,Open-Label Clinical Study to Evaluate the Safety and Efficacy of ABSK061 and ABSK043 with or without Chemotherapy in Patients with Metastatic/Unresectable Solid Tumors with FGFR2/3 Alterations（Protocol No: ABSK061-201）”.

ABSK061 is the world's most clinically advanced orally bioavailable, potent and selective inhibitor of FGFR2 and FGFR3. ABSK043 is a leading orally bioavailable, potent and selective inhibitor of PD-L1. In previous studies, both drugs demonstrated robust anti-tumor activity, a favorable safety profile, and low-risk of drug interaction, supporting the exploration of efficacy and safety of ABSK061 in combination with ABSK043 in advanced solid tumors with FGFR alterations.

ABSK061-201 is an open-label, multicenter, phase II clinical study designed to evaluate the safety and efficacy of the combination of ABSK061 and ABSK043 with or without chemotherapy in patients with metastatic/unresectable solid tumors harboring FGFR2/3 alterations. The study consists of two parts, a dose escalation and expansion phase. The dose escalation portion will assess safety, tolerability, preliminary efficacy, and the PK profile of ABSK061 + ABSK043 in patients with metastatic/unresectable advanced solid tumors with altered FGFR2/3 activation or overexpression to identify the recommended dose for the expansion phase.

The expansion phase will enroll tumor types with specific FGFR2/3 gene alterations, including HER2 negative gastric/gastroesophageal junction carcinoma, in multiple distinct solid tumor cohorts to evaluate the anti-tumor efficacy of ABSK061+ABSK043 with or without chemotherapy.

About ABSK061

ABSK061 is a novel, orally bioavailable, highly potent and selective small molecule inhibitor of FGFR2 and FGFR3 independently discovered and wholly owned by Abbisko Therapeutics. It is the first FGFR2/3 inhibitor to enter clinical trials globally. First-generation pan-FGFR inhibitors demonstrated clinical efficacy in multiple tumors carrying FGFR2/3 variants and have steadily gained regulatory approval globally. However, the therapeutic window of pan-FGFRs and their clinical efficacy have been limited by side effects associated with FGFR1 inhibition. By reducing FGFR1 activity while maintaining potency against FGFR2 and FGFR3, ABSK061 is expected to achieve a wider therapeutic window with improved clinical efficacy as a new-generation of FGFR inhibitors. In addition, ABSK061 has shown great potential to expand its use to a variety of non-oncology indications, including achondroplasia.

About ABSK043

ABSK043 is a novel, orally administered small molecule PD-L1 inhibitor displaying exceptional activity and high selectivity 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 restricting 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 available PD-1/PD-L1 small molecule drugs. ABSK043 is currently being studied in an ongoing Phase I clinical trial for advanced solid tumors in Australia and China.