A Study of Olverembatinib in SDH-deficient GIST.

A Single-Arm Registrational Phase III Study of Olverembatinib in the Treatment of Patients With SDH-Deficient Gastrointestinal Stromal Tumor (POLARIS-3)

An international multicenter, open, single-arm pivotal registration phase III study to determine the efficacy and safety of olverembatinib in patients with SDH-deficient gastrointestinal stromal tumor (GIST) who have previously been treated with one-line therapy, and to evaluate the progression-free survival and clinical benefit rate of olverembatinib in patients with SDH-deficient GIST.

Study Overview

• Status: Recruiting
• Conditions: GIST
• Intervention / Treatment: Drug: Olverembatinib

Detailed Description

This study intends to enroll patients with SDH-deficient GIST who have failed at least one systemic therapy to receive olverembatinib tablets 40mg orally administered with meals once every other day and every 28 days for a dosing cycle.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yifan Zhai, M.D., Ph.D.; Phone Number: +86-20-28068501; Email: yzhai@ascentage.com
• Study Contact Backup: Name: Chen Yang, M.D.; Email: Chen.Yang@ascentage.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-sen University Cancer Center
      • Contact: Ruihua Xu, M.D.,Ph.D.; Phone Number: 020-87343468; Email: xurh@sysucc.org.cn
      • Principal Investigator: Ruihua Xu, M.D.,Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically and/or cytologically confirmed GIST, immunohistochemistry with loss of SDHB expression, and failure of at least one prior systemic therapy. Defined as disease progression or intolerable as judged by the investigator.
2. Must have at least one measurable target lesion.
3. ECOG≤ 2.
4. Expected survival of at least 3 months.
5. Adequate organ function.
6. Negative serum pregnancy test result for women of childbearing potential within 7 days prior to taking the first dose of study drug.
7. Males, women of childbearing potential, as well as their partners, voluntarily take effective contraceptive measures as specified in the protocol from the time of signing the informed consent form until at least 30 days after the last dose of study drug.
8. Prior to initiation of any screening or study-specific procedures, the patient or his/her guardian is able to understand and voluntarily sign an informed consent form approved by the Ethics Committee in writing, voluntarily and able to complete the study procedures and follow-up examinations.

Exclusion Criteria:

1. Received antitumor cytotoxic chemotherapy, radiotherapy, biologic drug therapy, immunotherapy, or other investigational agents within 14 days or less than 5 times the half-life prior to the first dose.
2. Tyrosine kinase inhibitor (TKI) therapy within 7 days prior to the first dose.
3. Use of drugs that have drug interactions with the study drug within 7 days prior to the first dose.
4. Adverse events due to prior treatment have not recovered (> NCI CTCAE v5.0 Grade 1).
5. Absorption disorder syndrome or other conditions that affect the absorption of oral medications.
6. With clinically significant, uncontrolled or active cardiovascular disease or thrombotic disease.
7. Poorly controlled hypertension after hypertension medication.
8. Severe cardiovascular and cerebrovascular diseases during previous use of TKIs.
9. Uncontrolled Hyperlipidemia.
10. Major surgery, open biopsy, or major traumatic injury within 14 days prior to initiation of study drug.
11. With brain metastases.
12. Other malignancies within 2 years.
13. Uncontrolled systemic active fungal, bacterial, and/or viral infections.
14. Female patients who are pregnant or lactating, or female patients who are expecting to become pregnant within the period of this study.
15. Any symptoms or disease of the patient, in the judgment of the investigator or sponsor, that may jeopardize their safety or interfere with the safety evaluation of the investigational drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olverembatinib	Drug: Olverembatinib; Oral administration with meal, QOD, every 28 days for a cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival(PFS) rate	Proportion of subjects who do not experience disease progression or death after the first dose of treatment as assessed by Independent Review Committee.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.	According to CTCAE v5.0, the number and frequency of adverse events of test drug were assessed.	Through study completion,an average of 2 years.
Plasma concentrations of olverembatinib	Blood samples will be collected to measure the plasma concentration of olverembatinib.	Cycle 2 to Cycle 3 (each cycle is 28 days)

Collaborators and Investigators

• Sponsor: Ascentage Pharma Group Inc.
• Collaborators: HealthQuest Pharma Inc.
• Investigators: Study Chair: Ruihua Xu, M.D., Ph.D., Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2024
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): June 30, 2029

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 23, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: GIST; Olverembatinib
• Other Study ID Numbers: HQP1351GG301

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No