Olverembatinib for Chronic Myeloid Leukemia

(POLARIS-2 Trial)

Overseen By Kate Shantz

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ascentage Pharma Group Inc.

Must not be taking: Olverembatinib, Bosutinib

Disqualifiers: Active infection, GI disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

285 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, olverembatinib, for individuals with chronic myeloid leukemia, a type of blood cancer. Researchers aim to determine if olverembatinib is safe and more effective than bosutinib. The trial consists of two parts: one compares the two drugs, and the other focuses on olverembatinib in patients with a specific mutation (T315I). Individuals with chronic myeloid leukemia who have tried at least two other treatments may be suitable candidates for the trial. As a Phase 3 trial, this represents the final step before FDA approval, providing an opportunity to access a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that olverembatinib is generally well-tolerated by people with chronic myeloid leukemia (CML). Specifically, patients with the T315I mutation have demonstrated that this treatment is safe. Most individuals taking olverembatinib did not experience serious side effects.

Studies have found that patients with CML-CP (chronic phase chronic myeloid leukemia) who have tried several treatments before found olverembatinib to be both effective and safe.

Overall, while every treatment can have some side effects, evidence suggests that olverembatinib is relatively safe, especially for those who have already tried other options for CML. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for chronic myeloid leukemia?

Researchers are excited about olverembatinib for chronic myeloid leukemia (CML) because it targets the T315I mutation, which is a common resistance mutation in CML that doesn't respond well to standard treatments like imatinib, dasatinib, or nilotinib. Most existing therapies work by inhibiting BCR-ABL1, a protein that contributes to cancer cell growth, but struggle with the T315I mutation. Olverembatinib offers a new approach by effectively overcoming this mutation, providing hope for patients who have not responded to other tyrosine kinase inhibitors (TKIs). This makes olverembatinib a potentially powerful option for patients with limited alternatives.

What evidence suggests that this trial's treatments could be effective for chronic myeloid leukemia?

Research has shown that olverembatinib may effectively treat chronic myeloid leukemia (CML). In this trial, participants will join one of two parts: Part A, where olverembatinib is compared to bosutinib, and Part B, where olverembatinib is evaluated specifically for patients with the T315I mutation. Studies have found that olverembatinib works well for patients whose disease doesn't respond to other treatments, especially those with the T315I mutation. Patients in these studies experienced significant anti-leukemic effects, actively fighting leukemia cells. Olverembatinib is also generally well-tolerated, meaning most people can take it without severe side effects. This evidence suggests that olverembatinib could be a strong option for those with difficult-to-treat CML. ^{3 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Chronic Myeloid Leukemia (CML) who've already tried at least two approved treatments. For part of the study, participants must have a specific mutation (T315I). They should be in decent health and able to perform daily activities with ease. Pregnant or nursing women, those allergic to the study drugs or their ingredients, people with infections needing treatment, or those with gut conditions affecting drug absorption can't join.

Inclusion Criteria

I have been diagnosed with chronic myeloid leukemia in the chronic phase.

My organs are functioning well.

Written informed consent obtained prior to any screening procedures

Exclusion Criteria

I have never had an allergic reaction to bosutinib or its ingredients.

I am currently taking medication for an active infection.

My cancer has the T315I mutation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olverembatinib or bosutinib for 24 weeks to assess major molecular response (MMR) rate

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Olverembatinib

Trial Overview The trial is testing Olverembatinib against Bosutinib in patients with CML. It's an open-label study which means everyone knows what treatment they're getting. Participants are randomly assigned to one of the drugs and it's being conducted globally across multiple centers.

How Is the Trial Designed?

Group I: Part B, SAT, olverembatinib arm Experimental Treatment 1 Intervention

To evaluate the efficacy and safety of olverembatinib in the CML-CP patients with T315I mutation previously

Group II: Part A, RCT, olverembatinib arm and bosutinib arm Experimental Treatment 2 Interventions

Randomized controlled part that is designed to compare the efficacy and safety of olverembatinib (investigational arm) versus bosutinib (control arm) in patients with CML-CP, previously treated with at least two TKIs

Olverembatinib is already approved in China for the following indications:

Approved in China as Olverembatinib for:

• Chronic myeloid leukemia (CML) resistant to first- and second-generation TKIs
• Accelerated-phase CML (AP-CML) harboring the T315I mutation
• Chronic-phase CML (CP-CML) resistant to and/or intolerant of first- and second-generation TKIs

Who Is Running the Clinical Trial?

Ascentage Pharma Group Inc.

Lead Sponsor

Trials

54

Recruited

5,700+

Published Research Related to This Trial

In a study of 338 patients with chronic myeloid leukemia (CML), glivek therapy resulted in a high five-year survival rate of 89% for untreated patients and 88% for pretreated patients, indicating its effectiveness as a treatment.

The probability of achieving a complete cytogenetic response (CCR) was very high (96%) in untreated patients, while factors like blastemia and splenomegaly negatively impacted CCR in pretreated patients, highlighting the importance of early treatment for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prognosis factors in imatinib mesilate therapy in patients with a chronic phase of Ph-positive chronic myeloid leukemia: data from a multicenter non-randomized trial in Russia]. Zaritskiĭ, AIu., Lomaia, EG., Vinogradova, OIu., et al.[2015]

Olverembatinib is a novel oral tyrosine kinase inhibitor that effectively targets the T315I mutation in the BCR::ABL1 tyrosine kinase, which is a significant cause of resistance in chronic myeloid leukemia (CML) treatment.

Recent studies suggest that olverembatinib is a safe and effective treatment option for CML patients with the T315I mutation, addressing a critical challenge in managing this disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib in chronic myeloid leukemia. Öziskender, R., Eşkazan, AE.[2022]

Olverembatinib demonstrated significant antileukemic activity in adults with TKI-resistant chronic myeloid leukemia (CML), particularly in patients with the T315I mutation, with 3-year cumulative incidences of major cytogenetic response (MCyR) reaching 79% in chronic phase (CML-CP) and 47.4% in accelerated phase (CML-AP).

The treatment was well tolerated, with common side effects including skin hyperpigmentation and severe thrombocytopenia, indicating a manageable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. Jiang, Q., Li, Z., Qin, Y., et al.[2023]

Olverembatinib, a third-generation ABL tyrosine kinase inhibitor, shows promise in treating relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with the T315I mutation, which is typically resistant to most TKIs.

In two reported cases, the combination of olverembatinib and blinatumomab resulted in a safe and effective treatment, achieving minimal residual disease (MRD) negativity after just one cycle, suggesting a new chemo-free approach for managing relapsed or refractory Ph+ ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib combined with blinatumomab in treating T315I-mutated Philadelphia chromosome-positive acute lymphoblastic leukemia: two-case report. Fan, S., Wang, L., Lu, Y., et al.[2023]

Olverembatinib is a third-generation tyrosine kinase inhibitor specifically designed to target the T315I mutation, which is commonly associated with resistance to first- and second-generation TKIs in chronic myeloid leukemia (CML) patients.

Preliminary clinical data indicate that olverembatinib shows both safety and efficacy in treating CML patients who have the T315I mutation or who are resistant to previous TKI treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia. Qian, H., Gang, D., He, X., et al.[2022]

In a study of 118 chronic myeloid leukemia (CML) patients who were resistant or intolerant to previous treatments, bosutinib showed significant efficacy with a 32% major cytogenetic response and a 73% complete hematologic response after a median follow-up of 28.5 months.

Bosutinib demonstrated an acceptable safety profile, with mostly manageable side effects like gastrointestinal issues and rash, making it a promising treatment option for CML patients who have failed multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. Khoury, HJ., Cortes, JE., Kantarjian, HM., et al.[2022]

The BCR/ABL tyrosine kinase is identified as a key factor in chronic myeloid leukemia (CML), leading to the development of STI571 (imatinib mesylate) as a targeted treatment.

Phase I and II trials have demonstrated the efficacy of STI571 in treating CML, and the authors propose algorithms to assist in personalized treatment decisions for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[How I treat...chronic myeloid leukemia]. Hafraoui, K., Humblet-Baron, S., Baron, F., et al.[2015]

Bosutinib is an effective second-generation tyrosine kinase inhibitor for treating chronic myeloid leukemia, showing efficacy in pivotal clinical trials with dosages of 400mg daily for first-line treatment and 500mg daily for later lines of treatment.

Management of bosutinib-related adverse events, particularly gastrointestinal symptoms and liver toxicity, is crucial for maintaining patient safety and treatment effectiveness, prompting expert recommendations for optimal management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimizing the use of bosutinib in patients with chronic-phase chronic myeloid leukemia: Recommendations of a panel of experts from the Fi-LMC (French CML working group)]. Rea, D., Cayssials, E., Charbonnier, A., et al.[2023]

Olverembatinib (HQP1351) is a third-generation tyrosine kinase inhibitor specifically designed to target BCR-ABL1 mutations, including the T315I mutation that causes resistance to earlier treatments, making it a promising option for patients with chronic myeloid leukaemia (CML).

In November 2021, olverembatinib was approved in China for adult patients with TKI-resistant chronic-phase or accelerated-phase CML harboring the T315I mutation, indicating its efficacy in overcoming resistance that limits other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. Dhillon, S.[2022]

Citations

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Olverembatinib in chronic myeloid leukemia—review of ... Once considered imminently fatal (median survival 3–6 years), chronic myeloid leukemia (CML) is now managed with a diverse clinical ...

2. ascentage.com ascentage.com/ascentage-pharma-to-present-data-from-multiple-studies-of-olverembatinib-including-the-first-dataset-from-polaris-1-study-at-ash-2025/

Ascentage Pharma to Present Data from Multiple Studies of ... In patients with ND Ph+ ALL, olverembatinib in combination with chemotherapy demonstrated an MRD-negative CR rate of 64.2% by the end of the ...

3. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-022-01334-z

Olverembatinib (HQP1351), a well-tolerated and effective ... Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04260022

NCT04260022 | Study of HQP1351 in Subjects With ... RP2D of HQP1351 will be determined based on the comprehensive analyses of the PK, safety, and efficacy data of the US patients treated with HQP1351, when ...

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Olverembatinib (HQP1351) Demonstrates Efficacy Vs. Best ... Olverembatinib (HQP1351) demonstrates efficacy vs. best available therapy (BAT) in patients (Pts) with tyrosine kinase inhibitor (TKI)-resistant chronic ...

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Olverembatinib (HQP1351), a well-tolerated and effective ... Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06423911

Study of Olverembatinib (HQP1351) in Patients With CP-CML There are three types of violations: Failure to submit required clinical trial information; Submission of false or misleading clinical trial information ...

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Olverembatinib Demonstrates Efficacy and Safety in ... Olverembatinib demonstrated preliminary efficacy and was well tolerated in patients with heavily pretreated chronic-phase myeloid leukemia.