Olverembatinib for Chronic Myeloid Leukemia

(POLARIS-2 Trial)

Overseen By Huanshan Guo

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

Trial Summary

What is the purpose of this trial?

A Global Multicenter, Open Label, Randomized, Phase 3 Registrational Study of Olverembatinib (HQP1351) in Patients with Chronic Phase Chronic Myeloid Leukemia (POLARIS-2)

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.

What data supports the effectiveness of the drug Olverembatinib for chronic myeloid leukemia?

Olverembatinib has shown effectiveness in treating chronic myeloid leukemia (CML) patients with the T315I mutation, which makes them resistant to other treatments. Clinical studies have demonstrated that Olverembatinib is a safe and effective option for these patients, leading to its approval in China for TKI-resistant CML. ^{1 2 3 4 5}

Is Olverembatinib safe for humans?

Olverembatinib has been shown to be a generally safe treatment option for patients with chronic myeloid leukemia, particularly those with the T315I mutation, based on recent studies. It is well-tolerated, meaning most side effects are manageable and not severe. ^{1 2 3 6 7}

How is the drug Olverembatinib different from other treatments for chronic myeloid leukemia?

Olverembatinib is unique because it is a third-generation drug that can effectively target the T315I mutation in chronic myeloid leukemia, which makes the disease resistant to first- and second-generation treatments. It is taken orally and has shown promising results in patients who have not responded to other treatments. ^{1 2 3 8 9}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 (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]

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]

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]

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]

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]

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]

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, 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]

References

1. England 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. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Olverembatinib: First Approval. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

Olverembatinib in chronic myeloid leukemia. [2022]

4. Belgium pubmed.ncbi.nlm.nih.gov

[How I treat...chronic myeloid leukemia]. [2015]

5. Switzerland pubmed.ncbi.nlm.nih.gov

A review of the therapeutic role of the new third-generation TKI olverembatinib in chronic myeloid leukemia. [2022]

6. France 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)]. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Bosutinib is active in chronic phase chronic myeloid leukemia after imatinib and dasatinib and/or nilotinib therapy failure. [2022]

8. Russia (Federation) 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]. [2015]

9. Germany pubmed.ncbi.nlm.nih.gov

Olverembatinib combined with blinatumomab in treating T315I-mutated Philadelphia chromosome-positive acute lymphoblastic leukemia: two-case report. [2023]