Olverembatinib Plus Chemo Receives Breakthrough Therapy Designation in China for Newly Diagnosed Ph+ ALL

The Center for Drug Evaluation of China’s National Medical Products Administration has granted breakthrough therapy designation to olverembatinib (HQP1351) in combination with low-intensity chemotherapy for the first-line treatment of newly diagnosed patients with Philadelphia chromosome–positive (Ph-positive) acute lymphoblastic leukemia (ALL).1

Olverembatinib is the first third-generation BCR-ABL inhibitor to be approved in China, according to drug developer Ascentage Pharma.

“We are much encouraged to have olverembatinib’s clinical value once again recognized by the regulatory authority in China,” Yifan Zhai, MD, PhD, chief medical officer of Ascentage Pharma, stated in a news release. “This breakthrough therapy designation underscores the therapeutic potential and utility of olverembatinib in Ph-positive ALL, a hematologic malignancy with dismal prognosis. Moving forward, we will strive to accelerate this clinical development program for olverembatinib and bring it to more patients as quickly as possible.”

Previously reported findings from a single-arm, prospective, phase 2 trial (ChiCTR2200059682), which were presented at the 2023 ASH Annual Meeting, showed that olverembatinib plus reduced-intensity chemotherapy with vindesine and prednisone was a safe and effective regimen for patients with newly diagnosed Ph-positive ALL.2 Among efficacy evaluable patients (n = 25), the combination produced an overall response rate of 100%, including a complete remission (CR) rate of 96% and a CR with incomplete platelet recovery rate of 4%. At the time of data collection, 23 patients had completed 3 cycles of the regimen, and 82.6% of patients had achieved complete molecular remission (CMR). Of the remaining 6 patients, 1 attained CMR after 1 cycle, another after 2 cycles, and 4 were still undergoing induction therapy. The CMR rates at 4, 8, and 12 weeks were 36%, 76%, and 82.6%, respectively.

After a median follow-up of 241 days, 1 patient died within a month post-transplantation. All remaining patients survived without experiencing relapse. The most common any-grade adverse effects (AEs) in the safety-evaluable patient population (n = 29) were hematologic toxicities; these included anemia (79.3%), decreased white blood cell counts (96.5%), decreased neutrophil counts (96.5%), and decreased platelet counts (86.2%). The most frequent any-grade nonhematologic AE was liver function impairment, primarily elevated alanine aminotransferase levels (75.9%).

Current Olverembatinib Indications and Ongoing Investigations

In addition to the current designation, olverembatinib has received 2 other breakthrough therapy designations in China.1 The first, granted in March 2021, was for patients with chronic-phase chronic myeloid leukemia (CP-CML) that is resistant or intolerant to first- and second-generation TKIs; the agent was later approved for this indication. Additionally, in June 2023, olverembatinib received a breakthrough therapy designation for patients with succinate dehydrogenase–deficient gastrointestinal stromal tumors following first-line treatment.

Olverembatinib is also approved in China for adult patients with TKI-resistant CP-CML or accelerated-phase, T315I-mutant CML. All approved indications are included in the China National Reimbursement Drug List.

A global, multicenter, randomized-controlled, open-label, registrational phase 3 study (NCT06051409) is currently evaluating the efficacy and safety of olverembatinib in combination with chemotherapy in patients with treatment-naive, Ph-positive ALL.1,3

To enroll in this trial, patients are required to be at least 18 years of age, meet the World Health Organization 2016 diagnostic and typing criteria for Ph- or BCR/ABL1-positive ALL, and have an ECOG performance score of 2 or lower.3 Upon enrollment, they will receive either a once-daily dose of oral olverembatinib or imatinib (Gleevec) in addition to chemotherapy. The study’s primary end point is minimal residual disease negativity rate, with secondary end points including safety, pharmacokinetics, and patient-reported outcomes.

As of October 2023, the trial had dosed its first patient, according to Ascentage Pharma.4

References

1. Olverembatinib granted breakthrough therapy designation for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). News Release. Ascentage Pharma. March 5, 2025. Accessed March 6, 2025. https://ascentage.com/olverembatinib-granted-breakthrough-therapy-designation-for-the-treatment-of-philadelphia-chromosome-positive-ph-acute-lymphoblastic-leukemia-all/
2. Xu G, Lou Y, Huafeng W, et al. Combination of olverembatinib and VP regimen for newly diagnosed adult Philadelphia chromosome-positive acute lymphoblastic leukemia. Blood. 2023;142(suppl 1):4205. doi:10.1182/blood-2023-187130
3. A study of olverembatinib in patients with newly diagnosed Ph+ALL. ClinicalTrials.gov. Updated November 7, 2024. Accessed March 6, 2024. https://clinicaltrials.gov/study/NCT06051409
4. First patient dosed in the registrational phase III study of olverembatinib in treatment-naïve patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). News Release. Ascentage Pharma. October 17, 2023. Accessed March 6, 2025. https://www.ascentage.com/first-patient-dosed-in-the-registrational-phase-iii-study-of-olverembatinib-in-treatment-naive-patients-with-philadelphia-chromosome-positive-ph-acute-lymphoblastic-leukemia-all/