Safety and Efficacy of Lucitanib Plus Toripalimab in Advanced Solid Tumors Refractory to Standard Therapies: An Open-Label, Multicenter, Phase II Study.

Lucitanib is a novel multi-target inhibitor of vascular endothelial growth factor receptor 1-3, fibroblast growth factor receptor 1-3, and platelet-derived growth factor receptor α/β. This open-label, multicenter, single-arm Phase II study evaluated lucitanib plus the anti-programmed cell death 1 (PD-1) antibody toripalimab in patients with advanced solid tumors refractory to standard therapies. Patients received lucitanib (10 mg) once daily plus toripalimab (240 mg) every 3 weeks until progression or unacceptable toxicity. The primary endpoint was investigator-assessed objective response rate (ORR) and secondary endpoints included disease control rate, duration of response, progression-free survival (PFS), overall survival, and safety. Among 131 patients across four cohorts (PD-1-treated recurrent/metastatic nasopharyngeal carcinoma [NPC], PD-1-naïve NPC, recurrent/metastatic endometrial cancer [EC], and other tumors), ORR was 34.1%, 45.8%, 38.5%, and 13.5%, respectively. Median PFS was 4.2 months (95% confidence interval [CI], 4.1-5.6), 6.5 months (95% CI, 4.0-not estimable [NE]), 5.6 months (95% CI, 2.78-11.21), and 9.7 months (95% CI, 5.4-NE). The most common Grade ≥ 3 treatment-related adverse events were hypertension (37.4%), proteinuria (10.7%), and thrombocytopenia (10.7%). Lucitanib plus toripalimab showed encouraging antitumor activity with manageable safety in heavily pretreated advanced solid tumors, supporting further randomized evaluation, particularly in NPC and EC. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2400087935.