Olverembatinib and chemo show deep response in trial for Ph-positive ALL
Combo promising for those newly diagnosed with fast-growing blood cancer
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Olverembatinib (HQP1351), used in combination with low-intensity chemotherapy, has shown encouraging therapeutic potential — along with a favorable safety profile — in individuals with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL), a type of fast-growing blood cancer.
These new findings come from an initial dataset of the Phase 3 POLARIS-1 trial (NCT06051409), underway at sites in Australia and China. The trial, slated to run through 2028, is evaluating the safety and efficacy of olverembatinib plus chemotherapy in an estimated 350 previously untreated adults with Ph-positive ALL. First launched in China in 2023, the study is still enrolling patients 18 and older.
POLARIS-1 is designed as a registrational trial, meaning it is intended to generate sufficient clinical evidence to support potential regulatory approval of the therapy under investigation.
The interim data were presented in a poster titled “Results of POLARIS-1, a global phase 3 study (Part A): Olverembatinib combined with low-intensity chemotherapy in patients with newly diagnosed (ND) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL),” at this year’s American Society of Hematology (ASH) annual meeting, held earlier this month in Orlando, Florida.
“At ASH 2025, we presented the first dataset from the POLARIS-1 study that positioned olverembatinib as a highly promising potential new treatment option for patients with [Ph-positive] ALL,” Yifan Zhai, MD, PhD, chief medical officer of Ascentage Pharma, the therapy’s developer, said in a company press release.
Based on the therapy’s favorable clinical benefits and tolerability observed to date, the trial was given a green light earlier this month by both the U.S. Food and Drug Administration and the European Medicines Agency, a separate company press release noted. According to Ascentage, “the POLARIS-1 study is simultaneously enrolling patients across trial centers in multiple countries … to accelerate olverembatinib’s path to registration worldwide, particularly in the US and European markets.”
Additionally, Ascentage has entered into an exclusive option agreement with Takeda. If exercised, Takeda would obtain global rights to develop and commercialize olverembatinib outside mainland China, Hong Kong, Macau, and Taiwan.
Zhai said the company is “optimistic that Olverembatinib-based innovative regimens will bring a new paradigm to the treatment of [Ph-positive] ALL.”
In Ph-positive ALL, DNA pieces swap places, creating abnormal gene
ALL develops in the bone marrow and affects immature white blood cells. In Ph-positive ALL, pieces of DNA on chromosomes 9 and 22 swap places, creating a new abnormal gene called BCR-ABL1. This gene produces an abnormal tyrosine kinase protein that’s constantly active, driving uncontrolled growth.
Ph-positive leukemias are commonly treated with targeted therapies known as tyrosine kinase inhibitors (TKIs), which block the activity of the BCR-ABL1 protein and inhibit or slow the proliferation of cancer cells.
TKIs have transformed the treatment landscape for blood cancer. But first- and second-generation TKIs remain limited by high relapse rates, short disease-free survival, and suboptimal long-term outcomes, according to the company.
Jointly marketed by Ascentage Pharma and Innovent Biologics, olverembatinib is a third-generation TKI approved in China for several forms of chronic myeloid leukemia (CML) that are resistant to earlier-generation TKIs.
“Olverembatinib is emerging as a cornerstone in investigational combination chemotherapy regimens for patients with [Ph-positive] ALL,” said Suning Chen, PhD, a professor at The First Affiliated Hospital of Soochow University, who presented the study at ASH.
“It achieved both deep responses and low toxicity and therefore [has] the potential to bring a long-awaited new treatment to this indication,” Chen said.
Ongoing trial testing safety, effectiveness of olverembatinib
POLARIS-1 is testing the safety, tolerability, and efficacy of olverembatinib at two doses — 30 or 40 mg — when given orally every other day in combination with low-intensity chemotherapy. The combo is being compared to imatinib plus chemotherapy. Imatinib (sold as Gleevec, Imkeldi, and generics) is a first-generation TKI approved in the U.S. for use in certain cancers, including Ph-positive CML and Ph-positive ALL.
The trial’s main goal is to assess minimal residual disease (MRD) after three cycles of induction therapy. MRD refers to very small numbers of leukemia cells that may remain in the body after treatment and are not detectable using standard tests, but which can contribute to disease relapse.
Among the 53 patients evaluated in the first part of the study, the best MRD negativity rate was 66%, indicating that about two-thirds of patients had no detectable leukemia cells using sensitive molecular testing. By the end of induction therapy, 50 patients (94%) achieved a complete response (CR) or a CR with incomplete hematologic recovery, in which leukemia was no longer detectable but some blood cell counts remained low. Overall, 64% of patients achieved both a CR and MRD negativity.
Encouraging activity was also observed in patients with high-risk disease features. Among 10 patients carrying the IKZF1plus mutation — a genetic alteration associated with poorer outcomes and higher relapse risk in B-cell ALL, the most common form of ALL — nine (90%) achieved a molecular response by the end of induction therapy.
Data from the first part of the POLARIS-1 study … showed deep … responses in more than 60% of previously untreated patients with [Ph-positive] ALL who received Olverembatinib in combination with low-intensity chemotherapy. … These encouraging results validate olverembatinib’s global potential for reshaping the therapeutic landscape for [Ph-positive] ALL.
Olverembatinib plus low-intensity chemotherapy was generally well tolerated, and no significant differences in effectiveness or safety were observed between the olverembatinib 30 and 40 mg doses.
“We presented data [at ASH] from the first part of the POLARIS-1 study that showed deep MRD-negative responses in more than 60% of previously untreated patients with [Ph-positive] ALL who received Olverembatinib in combination with low-intensity chemotherapy, at the end of three induction cycles,” Chen said. “These encouraging results validate olverembatinib’s global potential for reshaping the therapeutic landscape for [Ph-positive] ALL.”
A separate global registrational Phase 3 trial, POLARIS-2 (NCT06423911), is also underway. It’s evaluating olverembatinib in CML.
