Journal for immunotherapy of cancer · 2026
BCL-2/BCL-xL inhibitor pelcitoclax with osimertinib for EGFR-mutated advanced non-small-cell lung cancer: a phase 1b trial.
СтатьяКлиническое исследование I фазыНазвание и аннотация: Перевод пока не подготовлен
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Ma Yuxiang, Wu Chunjiao, Zhao Yan-Qiu, Cui Jiuwei, Huang Yan, Fang Wenfeng, Yang Yunpeng, Zhao Yuanyuan, Yang Chen, Pan Wentao, Xiong Dengkun, Men Lichuang, Wang Hengbang, Yang Dajun, Zhai Yifan, Zhang Li, Zhao Hongyun
Аннотация
BACKGROUND: Overcoming tyrosine kinase inhibitor (TKI) resistance improves survival in advanced epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC). We therefore examined the safety and preliminary efficacy of pelcitoclax, a B-cell lymphoma-2 (BCL-2)/BCL-extra-large (BCL-xL) inhibitor, and osimertinib in patients with EGFR-mutated advanced NSCLC.
METHODS: Enrolled patients included Cohort 1 (previously progressed after third-generation TKI treatment+chemotherapy), Cohort 2 (previously progressed after first-generation or second-generation TKI treatment+chemotherapy), and Cohort 3 (TKI treatment-naive±prior chemotherapy). Patients received intravenous pelcitoclax (160 mg in dose-expansion and either 160 or 240 mg in dose-escalation) weekly and oral osimertinib 80 mg daily. Primary endpoints were safety and recommended phase 2 dose (dose-escalation), objective response rate (ORR) and safety (dose-expansion).
RESULTS: 64 patients were enrolled (13, dose-escalation; 51, dose-expansion): 29 patients in Cohort 1, 8 in Cohort 2, and 27 in Cohort 3. One dose-limiting toxicity occurred at pelcitoclax 240 mg, and the recommended phase 2 dose was 160 mg plus osimertinib 80 mg. The ORR was 10.7% and median progression-free survival (mPFS) 2.7 months in patients previously progressed after third-generation TKI treatment+chemotherapy (Cohort 1) and 80.8% and 16.4 months in TKI treatment-naïve patients±prior chemotherapy (Cohort 3). mPFS was longer in Cohort 1 patients with high expression of BCL-xL (4.2 vs 2.7 months, p=0.058).
CONCLUSIONS: Pelcitoclax combined with osimertinib showed promising safety and antitumor activity in EGFR-mutated NSCLC.
TRIAL REGISTRATION NUMBER: NCT04001777.
METHODS: Enrolled patients included Cohort 1 (previously progressed after third-generation TKI treatment+chemotherapy), Cohort 2 (previously progressed after first-generation or second-generation TKI treatment+chemotherapy), and Cohort 3 (TKI treatment-naive±prior chemotherapy). Patients received intravenous pelcitoclax (160 mg in dose-expansion and either 160 or 240 mg in dose-escalation) weekly and oral osimertinib 80 mg daily. Primary endpoints were safety and recommended phase 2 dose (dose-escalation), objective response rate (ORR) and safety (dose-expansion).
RESULTS: 64 patients were enrolled (13, dose-escalation; 51, dose-expansion): 29 patients in Cohort 1, 8 in Cohort 2, and 27 in Cohort 3. One dose-limiting toxicity occurred at pelcitoclax 240 mg, and the recommended phase 2 dose was 160 mg plus osimertinib 80 mg. The ORR was 10.7% and median progression-free survival (mPFS) 2.7 months in patients previously progressed after third-generation TKI treatment+chemotherapy (Cohort 1) and 80.8% and 16.4 months in TKI treatment-naïve patients±prior chemotherapy (Cohort 3). mPFS was longer in Cohort 1 patients with high expression of BCL-xL (4.2 vs 2.7 months, p=0.058).
CONCLUSIONS: Pelcitoclax combined with osimertinib showed promising safety and antitumor activity in EGFR-mutated NSCLC.
TRIAL REGISTRATION NUMBER: NCT04001777.