Phase 1b data support value of olverembatinib plus blinatumomab for relapsed or refractory CML-LBP or Ph–positive BCP-ALL

Olverembatinib, a third-generation tyrosine kinase inhibitor (TKI), combined with blinatumomab showed promising clinical activity and was generally well tolerated among patients with relapsed or refractory lymphoid blast phase chronic myeloid leukemia (CML-LBP) or Philadelphia chromosome (Ph)–positive B-cell precursor acute lymphoblastic leukemia (BCP-ALL) enrolled in a phase 1b trial.

Data from the trial, led by Elias Jabbour, MD, of The University of Texas MD Anderson Cancer Center, were presented at the 2026 American Society of Clinical Oncology Annual Meeting in Chicago, Illinois.

The study enrolled nine patients, eight with Ph–positive BCP-ALL and one with CML-LBP. The cohort’s median age was 47 years (range,32-60), median time from diagnosis to olverembatinib treatment initiation was 2.46 years (range, 0.5-6.2), median leukocyte count was 3.5×109 (range, 2-171), median prior regimens was four (range, 2-10), and median prior TKIs was three (range, 1-6). Seven patients had P190 BCR::ABL1 transcripts, two had P210 BCR::ABL1 transcripts, and one had T315I mutation. Notably, six patients had received prior blinatumomab and relapsed during maintenance or subsequent therapy.

The combination showed a manageable safety profile consistent with the known toxicities of each agent, with most reported adverse events (AEs) being grade 1 or 2. Four patients experienced grade 3 AEs related to olverembatinib, including increased lipase, neutropenia, thrombocytopenia, and pancreatitis. No dose-limiting toxicities occurred in the 30 mg every other day dose group, while one patient in the 40 mg group developed grade 3 treatment-related pancreatitis on day 4, which was resolved with supportive care and dose reduction to 30 mg.

With a median olverembatinib treatment duration of 15.7 weeks (range, 1.4-37.1), one patient discontinued due to disease progression and three discontinued to bridge to chimeric antigen receptor T-cell therapy or transplant. Among all nine patients, five had positive measurable residual disease (MRD) at baseline without complete response (CR). Of these, four achieved CR and two achieved MRD negativity after olverembatinib.

Overall, these findings support further investigation of this chemotherapy-free approach for patients with relapsed or refractory CML-LBP or Ph–positive BCP-ALL, Dr. Jabbour and colleagues wrote.

Reference
Jabbour E, Baer MR, Hunter A, et al. Olverembatinib (HQP1351) combined with blinatumomab in patients with lymphoid blast phase chronic myeloid leukemia (CML-LBP) or Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL). Abstract 6513. Presented at the 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago.

Watch: Dr. Elias Jabbour on olverembatinib in Ph-positive ALL and CML