## Protocol Section
### Identification Module
**NCT ID:** NCT06423911

**Acronym:** POLARIS-2

**Brief Title:** A Phase 3 Registrational Study of Olverembatinib (HQP1351) in Patients With CML

**Official Title:** This is a Global, Multi-center, Open-label Randomized and Registrational Phase 3 Study of Olverembatinib (HQP1351) in Patients With Chronic Myeloid Leukemia

#### Organization Study ID Info
**ID:** HQP1351CG301
#### Organization
**Class:** INDUSTRY
**Full Name:** Ascentage Pharma Group Inc.
### Status Module
#### Completion Date
**Date:** 2026-02

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** INDUSTRY

**Name:** Ascentage Pharma Group Inc.

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** True

**Oversight Has DMC:** True

### Description Module

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

**Detailed Description:** This is a global, multi-center, open-label randomized and registrational phase 3 study of olverembatinib: Part A is a 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 tyrosine kinase inhibitors (TKIs). Part B is to evaluate the efficacy and safety of olverembatinib in the CML- CP patients with T315I mutation.

### Conditions Module

**Conditions:**

- Chronic Myeloid Leukemia

- CML

- CML, Chronic Phase

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

**Intervention Model Description:** Part A 2:1 ratio Part B: control

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 285

**Type:** ESTIMATED

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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

**Intervention Names:**

- Drug: olverembatinib

- Drug: Bosutinib

**Label:** Arm A:

**Type:** OTHER

#### Arm Group 2

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

**Intervention Names:**

- Drug: olverembatinib

**Label:** Arm B:

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Arm A:

- Arm B:

**Description:** olverembatinib QOD

**Name:** olverembatinib

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Arm A:

**Description:** Bosutnib QD

**Name:** Bosutinib

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** To compare the major molecular response (MMR) rate at 24 weeks of olverembatinib versus bosutinib

**Measure:** MMR rate Part A

**Time Frame:** 24 weeks

**Description:** To evaluate the MMR rate by 24 weeks of olverembatinib in CML-CP patients with T315I mutation

**Measure:** MMR rate Part B

**Time Frame:** 24 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

Patients eligible for inclusion in this study must meet all of the following criteria.

1. Age ≥ 18 years old.
2. Diagnosis of CML-CP
3. Part A: Previously treated with at least two approved TKIs Part B: T315I mutation at screening.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
5. Written informed consent obtained prior to any screening procedures.
6. Patients with adequate organ functions

Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria.

1. For Part A only: T315I mutation at any time prior to starting study treatment.
2. Active infection that requires systemic drug therapy
3. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter absorption of study drugs
4. Previous treatment with or known / suspected hypersensitivity to olverembatinib or any of its excipients.
5. Previous treatment with or known / suspected hypersensitivity to bosutinib or any of its excipients.
6. Pregnant or nursing (lactating) women.

**Maximum Age:** 99 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** ben.little@ascentage.com

**Name:** Ben Little

**Phone:** 301-509-3222

**Role:** CONTACT

**Contact 2:**

**Email:** huanshan.guo@ascentage.com

**Name:** Huanshan Guo

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Houston

**Country:** United States

**Facility:** MD Anderson Cancer Center

**State:** Texas

**Zip:** 77030

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000009196

- Term: Myeloproliferative Disorders

- ID: D000001855

- Term: Bone Marrow Diseases

- ID: D000002908

- Term: Chronic Disease

- ID: D000020969

- Term: Disease Attributes

- ID: D000010335

- Term: Pathologic Processes

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: M18123

- Name: Leukemia, Myelogenous, Chronic, BCR-ABL Positive

- Relevance: HIGH

- As Found: Chronic Myeloid Leukemia

- ID: M18125

- Name: Leukemia, Myeloid, Chronic-Phase

- Relevance: HIGH

- As Found: CML, Chronic Phase

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M12149

- Name: Myeloproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M6147

- Name: Chronic Disease

- Relevance: LOW

- As Found: Unknown

- ID: M22700

- Name: Disease Attributes

- Relevance: LOW

- As Found: Unknown

- ID: T1303

- Name: Chronic Graft Versus Host Disease

- Relevance: HIGH

- As Found: Chronic

- ID: T3995

- Name: Myeloid Leukemia

- Relevance: HIGH

- As Found: Myeloid Leukemia

- ID: T1309

- Name: Chronic Myeloid Leukemia

- Relevance: HIGH

- As Found: Chronic Myeloid Leukemia

- ID: T1311

- Name: Chronic Myeloproliferative Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000007951

- Term: Leukemia, Myeloid

- ID: D000015464

- Term: Leukemia, Myelogenous, Chronic, BCR-ABL Positive

- ID: D000015466

- Term: Leukemia, Myeloid, Chronic-Phase

### Intervention Browse Module - Ancestors

- ID: D000092004

- Term: Tyrosine Kinase Inhibitors

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M42200

- Name: Bosutinib

- Relevance: HIGH

- As Found: Hydromorphone

- ID: M2889

- Name: Tyrosine Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: T22

- Name: Tyrosine

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: C000471992

- Term: Bosutinib

### Misc Info Module

- Version Holder: 2024-05-31
