CLTR-09 SYNERGISTIC EFFECT BETWEEN ACT001 AND WBRT/ICI IN NSCLC PATIENTS WITH BRAIN METASTASIS: THE INTERIM ANALYSIS OF A PHASE 2, MULTI-CENTER AND DOUBLE-BLIND RCT STUDY
Linlin Wang, Hui Wang, Xinhong Liu, Ruitai Fan, Zhihua Liu, Aiqin Gao, Yan Li, Hongtao Li, Liangfang Shen, Yuanyuan Zhou, Yongling Ji, Churong Li, Hongwei Li, Xiaozhi Zhang, Anwen Liu, Liting Qian, Suming Pan, Benhua Xu, Hong Yu, Gaoren Wang, Yue Chen, Dongpo Cai, Jinming YuAbstract
Background
Based on efficacy data from early phase study, the synergistic effect of ACT001 with WBRT/ICI was evaluated in expanded cohorts of NSCLC subjects.
Methods
Pretreated NSCLC with 4 or more metastatic brain lesions, most negative for driver mutations, were randomized with 2:1 ratio to ACT001 and Placebo cohorts and treated with WBRT and ACT001 or placebo at 400mg, BID followed by maintenance treatment. Concomitant ICI or chemotherapies were allowed. Brain MRI and CT scans were performed for intracranial and extracranial tumor assessments per RECIST 1.1 or RANO-BM criteria with intracranial ORR at 3-month after WBRT and OS as primary and secondary endpoints.
Results
32 and 17 NSCLC subjects including 78.1% and 88.2% with adenocarcinoma were randomly enrolled to ACT001 and Placebo cohorts. 71.9% and 70.5% subjects received at least two lines of prior anti-tumor treatments. Subjects were balanced in age, GPA/KPS and other baseline characteristics. 9 and 7 subjects took ICI in ACT001 and Placebo cohorts during study. With similar ratio of TEAEs and TRAEs reported in two cohorts, most common TRAEs were grade 1 or 2 events and related to laboratory, gastrointestinal and metabolic abnormalities in two cohorts. Comparable overall QLQ-C30 scores were observed in two cohorts within three months after WBRT. Improved intracranial ORRs were noted in FAS (25.0% in ACT001 vs 5.9% in Placebo, p = 0.0653), PPS (33.3% vs 7.7%, p = 0.0974) and IN-REAS (not shown). Although no OS improvement was noted in FAS, the ICI sub-group analysis revealed a trend of median OS improvement by ACT001: 11.4 vs 4.7 months, HR: 0.5, p = 0.2419.
Conclusion
Data from early and current trials revealed an encouraging synergistic effect between ACT001 and WBRT/ICI warranting in-depth efficacy assessment of ACT001, the first dual enhancer of ICI and genotoxic treatments through STAT3 and NF-κB inhibition, in newly diagnosed NSCLC patients.