Abstract CT225: Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study

Abstract Background: Surufatinib (S, a small-molecule inhibitor of VEGFR 1-3, FGFR1 and CSF-1R) plus toripalimab (T, an anti-PD-1 antibody) showed encouraging antitumor activity in solid tumors (Cao YS, 2022). Programmed death ligand 1 (PD-L1) expression is the established biomarker for 1L immune checkpoint inhibitors therapy in advanced NSCLC. We conducted an open-label, multi-cohort, single-arm phase 2 study to evaluate the safety and efficacy of S+T in patients (pts) with advanced solid tumors. Here, we reported the results of advanced NSCLC with PD-L1 positive expression cohort. Methods: Eligible pts had histologically confirmed advanced NSCLC with no prior systemic chemotherapy, PD-L1 positive (defined as PD-L1 TPS expression ≥1% [sp263]), and without EGFR, ALK or ROS1 genetic alteration if non-sq-NSCLC. Enrolled pts received 21-day cycles of S (250 mg orally QD) plus T (240 mg IV, Q3W) until disease progression or intolerable toxicity or the maximum duration of treatment with toripalimab is 24 months. The primary endpoint was objective response rate (ORR) per RECIST 1.1. Results: From July 2020 to September 2021, 55 pts were screened, of whom 23 pts were enrolled and received the treatment of S+T. Median age was 66 years (range: 49-73), 16 (69.6%) were male and 12 (52.2%) had squamous histology. Pts with PD-L1 TPS ≥50% and <50% were 10 and 13 respectively. At the data cutoff (Aug 31, 2022), the median follow-up duration was 13.1 mos. Among 21 pts with at least one post-baseline tumor assessment, the confirmed ORR was 57.1%, the median DOR was 8.31 mos, and DCR was 100%. Median PFS (mPFS) (95% CI) was 9.63 mos (5.49, -), median OS (mOS) (95% CI) was not reached (10.78, -), 12m-OS rate was 64%. According to PD-L1 level, the confirmed ORR were 66.7% and 50% for pts with PD-L1 TPS ≥50% and <50%, respectively; mPFS were 9.66 (0.69, -) and 6.93 mos (1.64, -), respectively; and the 12m-OS rate were 70% and 62%, respectively. mPFS did not differ with histology: 9.66 mos (5.49, -) for squamous cell carcinoma and 9.63 mos (0.69, -) for adenocarcinoma. All pts experienced ≥1 treatment emergent adverse event (TEAE). The most common Gr ≥3 TEAEs (≥5% pts) were aspartate aminotransferase increased (17.4%), malignant neoplasm progression (17.4%), hypokalemia (13.0%), hepatic function abnormal (13.0%), lymphocyte count decreased (8.7%), hypertension (8.7%) and pneumonitis (8.7%). Conclusion: Surufatinib and toripalimab combination showed a promising antitumor activity in 1L therapy for advanced PD-L1 positive NSCLC with manageable toxicity. This study might represent a potential treatment option for these pts. Clinical trial information: NCT04169672. Citation Format: Ying Cheng, Lin Shen, Zhendong Chen, Feng Ye, Xianjun Yu, Xing Zhang, Dongmei Ji, Baorui Liu, Lijie Song, Chunjiao Wu, Ming Lu, Wei Chen, Jingxun Wu, Heli Gao, Desheng Weng, Weina Shen, Rutian Li, Minjie Yang, Jinghong Zhou, Haiyan Shi, Panfeng Tan, Songhua Fan, Michael Shi, Weiguo Su. Surufatinib plus toripalimab for first-line treatment of advanced non-small cell lung cancer (NSCLC) with PD-L1 positive expression: A multicenter, single-arm phase 2 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT225.