OLVEREMBATINIB for Chronic myeloid leukemia (chronic phase)

Inclusion criteria

• {"criterion_text":"- Age ≥ 18 years old.\n- Adequate organ functions as defined below: • Creatinine clearance ≥30 mL/min as calculated using Cockcroft-Gault formula. • Total bilirubin < 1.5 × ULN except for patients with Gilbert’s syndrome who may only be included if total bilirubin ≤ 3.0 × ULN or direct bilirubin ≤ 1.5× ULN. • AST < 3 × ULN • ALT < 3 × ULN • Serum amylase ≤ 1.5 × ULN. For serum lipase ≤ 1.0 × ULN, value must be considered not clinically significant and not associated with risk factors for acute pancreatitis • Alkaline phosphatase ≤ 2.5 × ULN\n- Must have the following electrolyte values within normal limits or corrected to be within normal limits with supplements prior to first dose of study medication: • Potassium (potassium increase of up to 6.0 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits) • Total calcium (corrected for serum albumin); (calcium increase of up to 12.5 mg/dl or 3.1 mmol/L is acceptable at study entry if associated with creatinine clearance within normal limits)Magnesium, except for magnesium increase > ULN – 3.0 mg/dL; > ULN – 1.23 mmol/L associated with creatinine clearance (calculated using Cockcroft-Gault formula) within normal limits\n- Diagnosis of CML-CP according to CML NCCN Guidelines version 1.2024\n- Evidence of typical BCR::ABL1 transcript at the timing of screening which are amenable to standardized RQ-PCR quantification.\n- Must meet all the following laboratory values at the screening visit: • Peripheral blood myeloblasts < 15% • Peripheral blood myeloblasts and promyelocytes combined < 30% • Peripheral blood basophils < 20% • ≥ 50 × 109/L (≥ 50,000/mm3) platelets • Transient prior therapy related thrombocytopenia (<50,000/mm3 for ≤ 30 days prior to screening) is acceptable. • No evidence of extramedullary infiltrates of leukemia cells, except for hepatomegaly or splenomegaly\n- Part A: Prior treated with at least two approved TKIs, such as imatinib, nilotinib, dasatinib, radotinib, flumatinib, ponatinib, or asciminib\n- Part B: Patients must meet all three of the following criteria at screening. • Previously treated with at least one approved TKIs, such as imatinib, nilotinib, dasatinib, bosutinib, radotinib, flumatinib, ponatinib, or asciminib. • Have T315I mutation at screening. • There are no other effective and/or tolerable therapies available\n- Failure (adapted from the 2025 ELN Guidelines; Apperley et al, 2025) or intolerance to the most recent TKI therapy at the time of screening. • Failure is defined for CML-CP patients (CP at the time of initiation of last therapy) as follows. Patients must meet at least one of the following criteria. Three months after the initiation of therapy: BCR::ABL1 (IS) >10% and confirmed within 1-3 months. Six months after the initiation of therapy: BCR::ABL1 (IS) >10%. Twelve months after initiation of therapy: BCR::ABL1 (IS) >1% • At any time after the initiation of therapy, if new BCR::ABL1 mutations that cause resistance to current treatment are developed (refer to the latest version of the NCCN or ELN guidelines), and BCR::ABL1 (IS) > 0.1%. • At any time after the initiation of therapy, loss of response • At any time after the initiation of therapy, new clonal chromosome abnormalities in Ph+ cells: high risk ACA in Ph+ cells, and BCR>>ABL1 (IS) >0.1% • Intolerance is defined as below. Patients intolerant to the most recent TKI therapy must have BCR::ABL1 (IS) ratio more than 0.1% at screening.  Non-hematological intolerance: patients with grade 3 or 4 toxicity while on therapy, or with persistent grade 2 toxicity, unresponsive to optimal management, including dose adjustments (unless dose reduction is not considered in the best interest of the patient if response is already suboptimal)  Hematological intolerance: patients with grade 3 or 4 toxicity (ANC or platelets) while on therapy that is recurrent after dose reduction to the lowest doses recommended in label.\n- ECOG performance status (PS) ≤ 2.\n- Written informed consent obtained prior to any screening procedures."}

Exclusion criteria

• {"criterion_text":"- For Part A only: T315I or V299L mutation at any time prior to starting study treatment.\n- Plan to undergo allogeneic hematopoietic stem cell transplantation\n- Clinically significant, uncontrolled, or active cardiovascular disease, specifically including any of the following prior to starting study treatment: • Any history of myocardial infarction (MI) within 6 months. • Unstable angina within 3 months. • Any history of cerebrovascular accident within 1 year. • Transient ischemic attacks (TIA) within 3 months. • Any history of peripheral vascular or visceral infarction within 6 months. • Congestive heart failure (CHF) (New York Heart Association [NYHA] class III or IV) within 6 months. • Left ventricular ejection fraction (LVEF) less than lower limit of normal, per local institutional standards, within 6 months History of clinically significant atrial arrhythmia (such as atrial fibrillation with increased risk of thrombosis) or any history of ventricular arrhythmia (determined by the treating physician). • Venous thromboembolism, including deep venous thrombosis or pulmonary embolism, within 3 months prior to enrollment. Patients who have experienced a venous thromboembolic event should only be eligible if the condition is well controlled with optimal intervention (as determined by the treating physician). Continued prophylactic anticoagulation is acceptable. • Patients with revascularization procedures, including cardiac bypass within the 6 months and stenting within the past 3 months. • QTcF at screening ≥450 msec (male patients), ≥470 msec (female patients).\n- Presence of significant congenital or acquired bleeding disorder unrelated to CML\n- Another malignancy within 1 year prior to study entry. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection and are considered disease-free at the time of study entry\n- Active infection that requires systemic drug therapy, including active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection.\n- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of study drugs (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery).\n- (EU only) For Part A only: patient with impairment of hepatic function, which is contraindicated in the bosutinib Summary of Product Characteristics.\n- Treatment with medications that meet one of the following criteria and cannot be discontinued at least 7 days prior to the first dose of olverembatinib or bosutinib. • Moderate or strong inhibitors of CYP3A4 • Moderate or strong inducers of CYP3A4\n- Previous treatment with or known / suspected hypersensitivity to olverembatinib or any of its excipients\n- For Part A only: Previous treatment with or known / suspected hypersensitivity to bosutinib or any of its excipients\n- Participation in an investigational study within 30 days prior to randomization or within 5 half-lives of the investigational product, whichever is shorter\n- Pregnant or nursing (lactating) women\n- Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using adequate methods of contraception during dosing and for 4 months after last dose of olverembatinib and certain period according to the locally approved prescribing information for bosutinib. (Refer to protocol section 9.2.12.1 subsection pregnancy protection)\n- Prior diagnosis of CML AP or BP\n- Previous treatment with hematopoietic stem-cell transplantation."}

Primary endpoints

• {"endpoint_text":"- Part A: MMR rate at 24 weeks\n- Part B: MMR rate by 24 weeks","definition_or_measurement_approach":"MMR (major molecular response) assessed by standardized real‑time quantitative PCR (RQ‑PCR) quantification of BCR::ABL1 transcripts; reported as MMR rate at or by 24 weeks for each part."}

Secondary endpoints

• {"endpoint_text":"- Part A: MMR rate at 96 weeks\n- Part A: Cytogenetic response rate (complete, partial, major, minor, minimal, no response) at and by all scheduled data collection time points, including 24, 48 and 96 weeks\n- Part A: MMR, MR4, MR4.5 rate at all scheduled data collection time points (except 24 and 96 weeks which are already covered by primary and key secondary endpoints)\n- Part A: MMR, MR4, MR4.5 rate by all scheduled data collection time points including 24, 48 and 96 weeks\n- Part A: Time to MMR, MR4, MR4.5\n- Part A: Duration of MMR, MR4, MR4.5\n- Part A: Time to complete cytogenetic response (CCyR)\n- Part A: Duration of CCyR\n- Part A: Time to treatment failure\n- Part A: Progression free survival\n- Part A: OS\n- Part A: Type, frequency, and severity of adverse events\n- Part A: Changes in laboratory values that fall outside the normal ranges and clinically notable ECG and other safety data (vital signs, physical examination)\n- Part A: Trough plasma concentration; key PK parameters including apparent clearance, apparent volume of distribution and other appropriate parameters\n- Part A: Change in health utility from baseline over time according to EQ-5D-5L\n- Part A: Change in work productivity and activity impairment over time according to WPAI- GH\n- Part B: MMR rate by 96 weeks\n- Part B: Cytogenetic response rate (complete, partial, major, minor, minimal, no response) by all scheduled data collection time points, including 24, 48 and 96 weeks\n- Part B: MMR, MR4, MR4.5 rate by all scheduled data collection time points (except 24 and 96 weeks, which are already covered by primary and key secondary endpoints)\n- Part B: Time to MMR, MR4, MR4.5\n- Part B: Duration of MMR, MR4, MR4.5\n- Part B: Time to CCyR\n- Part B: Duration of CCyR\n- Part B: Time to treatment failure\n- Part B: Progression free survival\n- Part B: OS\n- Part B: Type, frequency, and severity of adverse events.\n- Part B: Changes in laboratory values that fall outside the normal ranges and clinically notable ECG and other safety data (vital signs, physical examination)\n- Part B: Trough plasma concentration; key PK parameters including apparent clearance, apparent volume of distribution and other appropriate parameters\n- Part B: Change in QoL from baseline over time according to EORTC QLQ-C30\n- Part B: Change in work productivity and activity impairment over time according to WPAI- GH\n- Part A: Change in Quality of Life (QoL) over time according to EORTC QLQ-C30\n- Part B: Change in health utility from baseline over time according to EQ-5D-5L","definition_or_measurement_approach":"Efficacy molecular endpoints (MMR, MR4, MR4.5) are assessed by standardized RQ‑PCR quantification of BCR::ABL1 transcripts. Cytogenetic response rates are assessed at scheduled time points (including 24, 48, 96 weeks) per protocol-defined cytogenetic assessments. Time-to-event endpoints (time to MMR/CCyR, time to treatment failure, PFS, OS) are measured from randomization/enrolment to the event. Safety endpoints (type, frequency, severity of AEs) are collected throughout treatment and follow-up (as reported in trial safety data); laboratory/ECG/vital signs monitored per schedule. PK endpoints: trough plasma concentrations and key PK parameters (apparent clearance, apparent volume of distribution, etc.) measured using plasma assays. QoL and health utility are measured using validated instruments: EQ-5D-5L (health utility) and EORTC QLQ-C30 (patient-reported QoL); work productivity measured by WPAI-GH."}

Poland

Earliest CTIS Part Ii Submission Date

15-01-2025

Latest Decision Or Authorization Date

24-02-2026

Processing Time Days

405

Number Of Sites

9

Number Of Participants

27

Italy

Earliest CTIS Part Ii Submission Date

09-12-2024

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

443

Number Of Sites

17

Number Of Participants

8

France

Earliest CTIS Part Ii Submission Date

20-12-2024

Latest Decision Or Authorization Date

26-02-2026

Processing Time Days

433

Number Of Sites

5

Number Of Participants

9

Germany

Earliest CTIS Part Ii Submission Date

14-01-2025

Latest Decision Or Authorization Date

13-03-2026

Processing Time Days

423

Number Of Sites

3

Number Of Participants

6

Belgium

Earliest CTIS Part Ii Submission Date

16-12-2024

Latest Decision Or Authorization Date

03-04-2026

Processing Time Days

473

Number Of Sites

6

Number Of Participants

8

Spain

Earliest CTIS Part Ii Submission Date

16-12-2024

Latest Decision Or Authorization Date

09-04-2026

Processing Time Days

479

Number Of Sites

16

Number Of Participants

10

Primary sponsor

Full Name

Ascentage Pharma Group Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Biotech Limited

Responsibilities

Sponsor duties codes: 1,10,11,12,2,5,6,8 (as listed in CTIS third-party entry)

Name

Almac Clinical Services Limited

Responsibilities

IP vendor (labeling, QP release and distribution)

Third parties

• {"country":"Spain","full_name":"Taxi Travel Ticket S.L.","duties_or_roles":"Patient reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"IP vendor (labeling, QP release and distribution)","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"Novasco","duties_or_roles":"Patient reimbursement","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"PK Lab kits and shipment logistics","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Molecularmd Corp.","duties_or_roles":"Sample storage","organisation_type":"Pharmaceutical company"}
• {"country":"China","full_name":"Zhejiang Taimei Medical Technology Co. Ltd.","duties_or_roles":"SUSAR support to Principal Investigators","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Icon Laboratory Services Inc.","duties_or_roles":"","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Iqvia Biotech Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}