Olverembatinib (HQP1351) is a third-generation BCR-ABL1 tyrosine kinase inhibitor developed by Ascentage Pharma. The drug was rationally designed to overcome resistance mutations, including the highly challenging T315I mutation, and has already demonstrated significant clinical activity in chronic myeloid leukemia (CML). Based on encouraging efficacy across multiple BCR-ABL1-driven malignancies, Ascentage is expanding olverembatinib into acute leukemias through the registrational Phase III POLARIS program.

POLARIS-1 is a global, multicenter Phase III study evaluating olverembatinib in combination with reduced-intensity chemotherapy in patients with newly diagnosed Ph+ ALL. The strategy reflects a broader shift in ALL management toward combining highly potent TKIs with less intensive chemotherapy to maximize molecular responses while limiting treatment-related toxicity. As of January 2026, 55 patients had been enrolled, with a median treatment duration of 11.6 months. The study population included patients with diverse BCR-ABL1 transcript variants, predominantly p190 disease, which represents the most common subtype in Ph+ ALL.

Safety Outcomes-

• All patients experienced ≥1 TEAE. Common TEAEs (≥20%) included neutropenia (76.4%), anemia (74.5%), hypokalemia (72.4%), leukopenia (70.9%), and thrombocytopenia (67.3%). 

• Grade ≥ 3 TEAEs (≥20%) included neutropenia (69.1%), thrombocytopenia (61.8%), leukopenia (60.0%), anemia (60.0%), pneumonia (34.5%), lymphocyte count decreased (23.6%), and hypokalemia (21.8%). 

• Two deaths from TEAEs were unrelated/unlikely to be related to olverembatinib. 

• One patient had Grade 2 coronary artery disease, possibly related to olverembatinib. 

• Treatment discontinuation was due to HSCT (9.1%), progression (7.3%), and/or toxicity (10.9%).

KOL Insights-

“The depth and rapidity of MRD responses observed in POLARIS-1 compare favorably with historical experiences using earlier-generation TKIs, particularly in patients with adverse-risk genomic features.”– Expert Opinion

“The clinical updates on olverembatinib presented at EHA 2026 further validate its therapeutic value in the global hematologic malignancy landscape. Olverembatinib has the potential to become an important treatment option for patients with CML, while also offering new therapeutic possibilities for those with Ph+ ALL. Looking ahead, we remain committed to accelerating the global clinical development of olverembatinib and exploring innovative treatment strategies to bring meaningful benefits to patients worldwide.”– Expert Opinion

Conclusion-

Ph+ ALL accounts for approximately 20–30% of adult ALL cases and historically represented one of the highest-risk ALL subtypes due to frequent relapse and poor long-term survival. The incorporation of BCR-ABL1 tyrosine kinase inhibitors has dramatically improved outcomes, but achieving deep molecular remissions remains critical because MRD negativity strongly correlates with long-term survival and reduced relapse risk.

The updated Phase III POLARIS-1 data demonstrate that olverembatinib combined with reduced-intensity chemotherapy induces rapid and deep molecular responses in newly diagnosed Ph+ ALL. The high MRD-negative CR rate, sustained increase in MRD negativity over time, and encouraging activity in adverse genomic subgroups such as IKZF1plus support the therapeutic potential of this next-generation TKI. If longer-term follow-up confirms durable remissions and favorable survival outcomes, olverembatinib could emerge as an important new frontline treatment option in Ph+ ALL.