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.

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.

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.