Phase 1 Trial of BCL-2 Inhibitor Lisaftoclax (APG-2575) in Chinese Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma and Other Non-Hodgkin Lymphomas.

[BACKGROUND] Lisaftoclax is a novel BCL-2 inhibitor. This phase 1 trial (NCT03913949) evaluated the safety and preliminary efficacy of lisaftoclax in Chinese patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and other non-Hodgkin lymphomas (NHL).

[PATIENTS AND METHODS] Lisaftoclax was administered orally in 28-day cycles, targeting daily doses of 20-800 mg for up to 24 cycles, using a daily ramp-up to minimize tumor lysis syndrome (TLS) risk. Patients with previous resistance to a BCL-2 inhibitor or exposure to a BCL-2 inhibitor in the most recent treatment line were excluded. Among 51 enrolled patients, 14 had CLL/SLL, 13 mantle cell lymphoma (MCL), and 4 marginal zone lymphoma (MZL).

[RESULTS] The maximum tolerated dose of lisaftoclax was not reached; neither dose-limiting toxicity nor TLS was observed. Common adverse events included anemia, neutropenia, and thrombocytopenia. Significant antitumor activity was observed in CLL/SLL (overall response rate [ORR] 71.4%, complete response [CR] 28.6%); MCL (ORR 50.0%, CR 20.0%); and MZL (ORR 50.0%, CR 0). Median progression-free survival was 7.9 (95% CI, 4.9-14.1) months for all patients and 18.6 (95% CI, 8.4-not reached [NR]) and 7.9 (95% CI, 2.0-NR) months for those with CLL/SLL and MCL, respectively. The median overall survival was NR (95% CI, 26.2-NR) for all patients.

[CONCLUSION] Lisaftoclax has a manageable safety profile and induces durable responses in R/R CLL/SLL and NHL.