PD-(L)1×VEGF双特异性抗体在实体瘤中的应用：来自ASCO 2026的临床试验更新。
完整摘要 · 中文译文
PD-(L)1×VEGF双特异性抗体在单一分子中整合了免疫检查点阻断与VEGF抑制，为克服血管生成相关免疫耐药提供了一种潜在策略。在2026年ASCO年会上，随机3期HARMONi-6试验表明，在既往未治疗的晚期鳞状非小细胞肺癌（NSCLC）患者中，依沃西单抗联合化疗较替雷利珠单抗联合化疗具有总生存获益，将生存证据扩展至以活性PD-1为基础的一线对照方案。pumitamig、SSGJ-707和HB0025的探索性2期研究在一线NSCLC中报告了令人鼓舞的活性，而IMM2510及基于依沃西单抗方案的1期和2期研究提示在既往接受过免疫治疗后仍具有活性。较小规模的探索性研究还报告了在围手术期头颈部癌、结直肠癌、子宫内膜癌和黏膜黑色素瘤中的活性。总体而言，这些发现凸显了PD-(L)1×VEGF双特异性抗体的临床潜力，其中最强证据见于一线鳞状NSCLC，更广泛的应用仍处于产生假设阶段。未来开发应优先关注预测性生物标志物、耐药机制、最佳治疗序贯以及免疫相关和VEGF相关毒性的审慎评估。
完整摘要 · 英文原文
PD-(L)1×VEGF bispecific antibodies integrate immune checkpoint blockade and VEGF inhibition within a single molecule, offering a potential strategy to overcome angiogenesis-associated immune resistance. At the 2026 ASCO Annual Meeting, the randomized phase 3 HARMONi-6 trial demonstrated an overall survival benefit with ivonescimab plus chemotherapy over tislelizumab plus chemotherapy in previously untreated advanced squamous non-small cell lung cancer (NSCLC), extending survival evidence to an active PD-1-based first-line comparator. Exploratory phase 2 studies of pumitamig, SSGJ-707, and HB0025 reported encouraging activity in first-line NSCLC, while phase 1 and 2 studies of IMM2510 and ivonescimab-based regimens suggested activity after prior immunotherapy. Smaller exploratory studies also reported activity in perioperative head and neck cancer, colorectal cancer, endometrial cancer, and mucosal melanoma. Collectively, these findings highlight the clinical potential of PD-(L)1×VEGF bispecific antibodies, with the strongest evidence in first-line squamous NSCLC and broader applications remaining hypothesis-generating. Future development should prioritize predictive biomarkers, resistance mechanisms, optimal treatment sequencing, and careful assessment of immune-related and VEGF-associated toxicities.