Abstract 134P
Background
Vascular endothelial growth factor (VEGF) inhibition may reverse suppressive microenvironment and recover sensitivity to subsequent immune checkpoint inhibitors (ICIs).
Methods
This is a phase Ib/IIa, single-arm study, comprising dose finding (Part A) and expansion cohort (Part B). Immune checkpoint-inhibitor refractory NSCLC were enrolled. The first 21-day treatment cycle was a safety observation period (phase Ib) followed by a phase II expansion cohort (nivolumab 360mg, every 3 weeks, plus anlotinib, RP2D, 14 days on and 7 days off). The primary objective is recommended phase 2 dose (RP2D, part A) safety (part B) and ORR (part B), respectively.
Results
Between November 2020 and March 2022, 35 patients were screened and 21 eligible patients were enrolled (6 patients in Part A). The PR2D is anlotinib 12 mg/day orally (14 days on and 7 days off) and nivolumab (360mg every 3 weeks). Adverse events of any cause and treatment-related were reported in all patients. Two patients (9.5%) experience grade 3 TRAE. No grade 4 or higher adverse events were observed. Serious adverse were reported in 4 patients. There were 6 and 4 patients experience anlotinib and nivolumab disruption due to TRAE. Dese reduction to 10mg at any time was required in 5 patients and no patients decreased to 8mg. ORR and DCR was 19.0% and DCR is 76.2%, respectively. Median PFS and OS were PFS was 7.43 months (95% CI, 4.54-10.21m) and 19.1months (95% CI, 10.37-NE).
Conclusions
Our study suggested that full dose anlotinib combined with nivolumab showed positive safety and efficacy signal. Further study is warranted.
Clinical trial identification
NCT04507906.
Legal entity responsible for the study
Baohui Han.
Funding
This work was supported by Shanghai Committee of Science and Technology (Project No. 21Y11913800), National Natural Science Foundation of China (Project No.82072573). Study drugs were provided by Bristol Myers Squibb and Jiangsu Chia Tai Tianqing Pharmaceutical Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.