Olverembatinib (BCR::ABL1 TKI) + blinatumomab (CD19 BiTE) delivers early CR/MRD clearance in heavily pretreated Ph+ ALL/CML-LBP

Olverembatinib (HQP1351) is a third-generation BCR::ABL1 tyrosine kinase inhibitor (active against resistant clones including T315I) combined here with blinatumomab, a CD19×CD3 bispecific T-cell engager, in the Phase 1b HQP1351CU101 trial (NCT04260022) in adults with R/R Ph+ BCP-ALL or CML lymphoid blast phase treated outside China (n=9; 8 Ph+ BCP-ALL, 1 CML-LBP; median 4 prior regimens, 3 prior TKIs; 6 had prior blinatumomab and relapsed). At 30mg QOD (n=3) there were no DLTs; at 40mg QOD, 1 DLT (grade 3 pancreatitis day 4) resolved with supportive care and dose reduction; other grade 3 olverembatinib-related AEs included increased lipase, neutropenia, and thrombocytopenia; 1 death occurred from progression (unrelated). Among the 5 patients MRD+ and not in CR at baseline, 4 achieved CR and 2 achieved MRD negativity by flow—directionally supportive in a post–blinatumomab-exposed population, though benchmarking is tricky given the tiny n and mixed baselines; for context, chemo-free ponatinib+blinatumomab has produced high molecular response rates in Ph+ ALL (including R/R cohorts in a single-center Phase 2), setting a high bar for “TKI+BiTE” combinations in this biology.