Phase 1b/2 study of surufatinib in combination with docetaxel as second-line treatment of advanced driver-gene negative non-squamous non-small cell lung cancer (NSCLC).

person Wei Jiang Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, China info_outline Wei Jiang, Jianbo He, Ruiling Ning, Yun Zhao, Shaozhang Zhou, Huilin Wang, Shubin Chen, Haijie Gan, Jieqing Lin, Qitao Yu

Authors person Wei Jiang Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, China info_outline Wei Jiang, Jianbo He, Ruiling Ning, Yun Zhao, Shaozhang Zhou, Huilin Wang, Shubin Chen, Haijie Gan, Jieqing Lin, Qitao Yu Organizations Department of Respiratory Oncology, Guangxi Medical University Cancer Hospital, Nanning, China, Guangxi Medical University Cancer Hospital, Nanning, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Hutchison Medipharma Limited Background: Advanced driver-gene negative non-squamous NSCLC has few second-line treatment choices. Surufatinib is a new antiangiogenic drug that potently inhibits VEGFR1，2，3, FGFR1 and CSF-1R. The purpose of this trial was to determine the recommended phase 2 dose of surufatinib in combination with docetaxel through a phase 1b study and to further analyze the preliminary efficacy and safety of the combination therapy in patients with advanced driver-gene negative non-squamous NSCLC. Methods: Advanced driver-gene negative non-squamous NSCLC patients progressed after first-line platinum-based chemotherapy (the combination with immune checkpoint inhibitors and/or bevacizumab was allowed) were enrolled to treat with surufatinib in combination with docetaxel. Using a 3 + 3 study design in the phase 1b dose-escalation portion, patients received surufatinib at doses ranging from 200 mg/day to 300 mg/day for 21 days per cycle. Surufatinib was started at a dose of 250 mg/day and exploratory dose of 300 mg/day if no patients develop dose-limiting toxicity (DLT) in the first 3 patients in the first treatment cycle. If 2 or more of the 3 patients develop DLT, exploratory dose of 200 mg/day. Concomitant treatment with docetaxel at a dose of 60 mg/m 2 . The primary objective of the study was the recommended phase 2 dose of surufatinib in combination with docetaxel. The secondary objective was the preliminary efficacy and safety. Results: At data cut-off (December 31, 2022), we recruited 9 patients in phase 1b portion. Three patients were enrolled in the surufatinib 250 mg/day dose cohort. Among them, 2 developed DLT (1 patient with grade 3 oral mucositis and 1 patient with grade 3 elevated blood bilirubin) which did not recur with a reduction of dosage to 200 mg/day. A total of 6 patients were enrolled in the 200 mg/day dose cohort and 1 patient developed DLT (grade 3 diarrhoea). The recommended phase 2 dose was established as surufatinib 200 mg/day combined with docetaxel 60 mg/m 2 .At present, there were 3 patients enrolled in phase 2. Among the 12 patients enrolled in this study, 1 patient was lost and 11 patients were assessable for treatment efficacy and safty. The objective response rate (ORR) was 27.2% (3/11) and the disease control rate (DCR) was 100%. The median progression free survival (PFS) was 5.8 months (95% CI = 2.1-9.4). The most common treatment-related adverse events (AEs) were diarrhoea (33.3%), neutropenia (41.7%), hypertension (25%), and anaemia (33.3%). Common grade 3 AEs included diarrhoea (16.7%), neutropenia (33.3%) and anaemia (16.7%), with no unexpected treatment-related AEs (TRAEs). Conclusions: Surufatinib in combination with docetaxel was an effective second-line treatment for patients with advanced driver-gene negative non-squamous NSCLC. The clinical benefit was encouraging, and the safety profile was acceptable. Clinical trial information: ChiCTR2100047313.

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