Olverembatinib for Chronic Myelogenous Leukemia

Overseen By Fadi Haddad, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Cardiac disease, Bleeding disorders, Psychiatric disorders, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 36 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if the drug olverembatinib can help manage chronic myelogenous leukemia (CML) in its early chronic phase. Participants will take olverembatinib every other day to assess its effectiveness. Suitable candidates for this trial are those recently diagnosed with CML, specifically the type that tests positive for certain genetic markers (Ph-positive or BCR::ABL1 positive), and who have not been treated with specific cancer drugs for more than 30 days. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on an FDA-approved TKI, you must not have taken it for more than 30 days to be eligible.

Is there any evidence suggesting that olverembatinib is likely to be safe for humans?

Research shows that olverembatinib is generally well tolerated by patients with chronic-phase myeloid leukemia (CML). Previous studies found that it works well and is tolerated even by patients who have tried many other treatments. While some side effects were reported, most patients in these studies managed them effectively. This suggests that olverembatinib could be a safe option for those considering participation in a clinical trial for CML. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Olverembatinib is unique because it targets the BCR-ABL mutation in chronic myelogenous leukemia (CML) with a new mechanism of action. Unlike standard treatments like imatinib, dasatinib, and nilotinib, which are also tyrosine kinase inhibitors, olverembatinib is designed to be effective against certain resistant mutations that can develop during treatment. Researchers are excited about its potential to overcome resistance and offer a new option for patients who don't respond well to existing therapies. Additionally, its oral administration every other day provides convenience and could improve patient compliance.

What evidence suggests that olverembatinib might be an effective treatment for chronic myelogenous leukemia?

Research has shown that olverembatinib, the treatment under study in this trial, may effectively treat chronic myelogenous leukemia (CML). Studies have found that it helps many patients achieve significant treatment goals, such as a major reduction in cancer cells (MMR) and a complete response in bone marrow tests (CCyR), particularly in those unresponsive to other treatments. Specifically, one study found that 82.68% of patients who had tried other drugs reached CCyR. Another study demonstrated that olverembatinib significantly improved survival rates for CML patients. These findings suggest that olverembatinib could be a promising option for managing newly diagnosed CML. ^{1 6 7 8 9}

Who Is on the Research Team?

Fadi Haddad, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults (≥18 years) with newly diagnosed chronic myeloid leukemia in the chronic phase can join. They must be willing to use birth control and have not had extensive prior treatments for CML. Participants need to have good organ function, no severe heart issues or psychiatric disorders, and cannot be pregnant.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and 4 months after completion of olverembatinib administration

Approved methods of birth control include hormonal contraception, intrauterine device (IUD), tubal ligation or hysterectomy, participant post vasectomy, implantable or injectable contraceptives, and condoms plus spermicide

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to olverembatinib or other agents used in study

Participants with active, uncontrolled psychiatric disorders including psychosis, major depression, and bipolar disorders

Participants who are receiving any other investigational agents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive olverembatinib monotherapy at a dose of 30 mg orally every other day

36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Olverembatinib

Trial Overview The trial is testing olverembatinib as a single therapy to see if it controls chronic myeloid leukemia in its early stage. It's for patients who haven't received much previous treatment and are now trying this medication for the first time.

How Is the Trial Designed?

Group I: Treatment with Olveremebatinib Experimental Treatment 1 Intervention

Patients will receive single agent olverembatinib at a dose of 30 mg orally every other day (QOD)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Ascentage Pharma Group Inc.

Industry Sponsor

Trials

54

Recruited

5,700+

Published Research Related to This Trial

In a study of 450 patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with tyrosine kinase inhibitors (TKIs) from 2004 to 2014, the 5-year overall survival rate was 95.1%, indicating high efficacy of TKIs in this patient population.

Severe adverse events (AEs) during first-line TKI therapy were linked to lower overall survival and event-free survival rates, suggesting that timely modifications to treatment are crucial when patients experience significant AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Severe adverse events by tyrosine kinase inhibitors decrease survival rates in patients with newly diagnosed chronic-phase chronic myeloid leukemia. Ota, S., Matsukawa, T., Yamamoto, S., et al.[2022]

Imatinib, a targeted inhibitor of the BCR-ABL fusion protein, has significantly improved survival rates for patients with chronic myelogenous leukemia (CML), but some patients develop resistance or intolerance to this therapy.

Second-generation tyrosine kinase inhibitors like nilotinib and dasatinib, along with newer options like ponatinib and bosutinib, provide additional treatment choices for CML, enhancing patient outcomes and quality of life, and ongoing clinical trials are exploring the best ways to use these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential therapy in chronic myelogenous leukemia: where do emerging therapies fit within current treatment regimens? Mauro, MJ., Talpaz, M., Radich, JP.[2017]

In a long-term study with a median follow-up of 10.9 years, imatinib demonstrated a high overall survival rate of 83.3% in patients with chronic myeloid leukemia (CML), indicating its sustained efficacy as an initial treatment.

Serious adverse events related to imatinib were rare and mostly occurred within the first year of treatment, suggesting that long-term use of imatinib is safe and does not lead to unacceptable cumulative toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of Imatinib Treatment for Chronic Myeloid Leukemia. Hochhaus, A., Larson, RA., Guilhot, F., et al.[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]

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 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]

In a study of 81 patients with chronic myeloid leukemia (CML) treated with imatinib over two years, 326 adverse drug reactions (ADRs) were reported, with hematological toxicities being the most common, particularly thrombocytopenia at 21.17%.

Most ADRs were classified as mild to moderate, indicating that while imatinib can cause significant side effects, they are generally manageable, highlighting the need for careful monitoring to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse drug reactions of imatinib in patients with chronic myeloid leukemia: A single-center surveillance study. Francis, J., Palaniappan, M., Dubashi, B., et al.[2020]

In a cost-effectiveness analysis involving 100 patients with chronic myeloid leukemia, nilotinib was found to provide more progression-free life-years saved (15.21) compared to imatinib (12.64) and dasatinib (14.91), indicating its superior efficacy as a first-line treatment.

Nilotinib was also shown to be more cost-effective than dasatinib, with a lower incremental cost-effectiveness ratio of US$ 33,120.36 per progression-free life-year saved, making it the preferred option for treatment in Colombia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012. Romero, M., Chávez, D., De Los Ríos, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12532375/

Olverembatinib in chronic myeloid leukemia—review of ... Since the introduction of the 1G TKI imatinib in 2000, the annual CML-attributable mortality has declined from 10%–20% to 1%. The prevalence is ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2531137924011672

EFFICACY OF OLVEREMBATINIB IN THE TREATMENT ... The results demonstrate that Olverembatinib has significant efficacy in achieving high rates of MMR, CCyR and MCyR in refractory CML patients.

3. 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 ... Conclusion: In patients with ND Ph+ ALL, olverembatinib in combination with chemotherapy demonstrated an MRD-negative CR rate of 64.2% by the ...

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/480/530696/Olverembatinib-As-Second-Line-2L-Therapy-in

Olverembatinib As Second-Line (2L) Therapy in Patients (pts ... In 32 efficacy-evaluable pts, 23 pts were pretreated with 2G TKIs as 1L treatment, of whom 19 (82.68%) achieved CCyR and 10 (43.5%) achieved MMR ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41098110/

Olverembatinib in accelerated-phase chronic myeloid ... The 6-year probabilities of transformation-free survival (TFS), CML-related survival and survival were 81% (72, 90%), 76% (67, 87%) and 71% (61, ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3151/529580/Olverembatinib-HQP1351-Overcomes-Resistance

Olverembatinib (HQP1351) Overcomes Resistance ... This update presents efficacy and safety data ... Exposure-Response (E-R) Analysis of Olverembatinib (HQP1351) in Chinese Patients with Chronic ...

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

Study of Olverembatinib (HQP1351) in Patients With CP-CML A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

8. onclive.com onclive.com/view/olverembatinib-demonstrates-efficacy-and-safety-in-heavily-pretreated-cp-cml

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

9. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper204996.html

Paper: Olverembatinib As Second-Line (2L ... The aim of this study was to assess the efficacy and safety of olverembatinib as a 2L treatment for pts with CP-CML without the T315I mutation.