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

ABSTRACT 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