Treatment with olverembatinib plus lisaftoclax yielded rapid, deep responses in children and adolescents with relapsed or refractory Philadelphia chromosome (Ph)–positive acute lymphoblastic leukemia who failed previous tyrosine kinase inhibitor therapy, according to phase 1b data presented at the Fourteenth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.
The chemotherapy-free oral regimen showed both central nervous system penetration and activity across ABL1 mutants, supporting its potential for this high-risk pediatric patient population, wrote the study’s authors, led by Jingliao Zhang, MD. Dr. Zhang is medical researcher and hematologist at the Institute of Hematology and Blood Diseases Hospital of the Chinese Academy of Medical Sciences and Peking Union Medical College in Tianjin, China.
The findings were presented at the Fourteenth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas, and the research was awarded first place during the abstract award ceremony at the meeting.
The study enrolled patients aged less than 18 years with relapsed or refractory Ph–positive ALL resistant or intolerant to one or more prior TKIs. Participants received monotherapy with olverembatinib, a third-generation TKI against BCR-ABL1, followed by combination therapy with lisaftoclax, a selective BCL-2 inhibitor, plus dexamethasone. The cohort consisted of 17 patients with a median age of 13 years (range, 9-15). Six out of 15 evaluable patients carried baseline ABL1 kinase domain mutations, including four with T315I mutation. A total of 16 patients received combination therapy.
The overall response rate among nine evaluable patients after olverembatinib monotherapy was 55.6%, increasing to 88.9% on day 15 of cycle two (C2D15). The rate of complete cytogenetic response after olverembatinib monotherapy was 40%, increasing to 88.9% at C2D15. The rate of measurable residual disease negativity after olverembatinib monotherapy was 25%, increasing to 66.7% at C2D15. By day 28 of cycle two, 93.3% of patients achieved a major molecular response or better.
Responses occurred across dose levels and ABL1 variants, and pharmacokinetic analyses showed predictable exposure comparable to adults, no significant accumulation or drug to drug interactions, and CNS penetration by both olverembatinib and lisaftoclax, according to the investigators.
Reference
Zhang J, Wang J, Liu T, et al. Safety and Preliminary Efficacy of Olverembatinib (HQP1351) Combined With Lisaftoclax (APG-2575) in Children and Adolescents With Relapsed/Refractory Philadelphia-Positive Acute Lymphoblastic Leukemia: Results of a Phase 1b Study. Abstract ALL-584. Presented at the 2026 Society of Hematologic Oncology Annual Meeting; September 9-12, 2026; Houston.
See Also: Phase 1b trial reports promising outcomes with olverembatinib plus blinatumomab in R/R CML or ALL
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