Efficacy and Safety of NB003 in Patients With Advanced Gastrointestinal Stromal Tumors (GIST)

Exclusion Criteria24

• Part 1: Participants who have received prior treatment with NB003 or regorafenib. Part 2: Participants who have received prior treatment with NB003 or sunitinib.
• Participants who have received any systemic anti-tumor therapy within 7 days prior to enrollment.
• Participants who have undergone major surgery (excluding vascular access placement, tumor biopsy, and feeding tube placement) or major palliative interventions (such as transarterial chemoembolization) within 4 weeks prior to enrollment.
• Participants who have received radiation therapy to >30% of the bone marrow or extensive radiation therapy within 4 weeks prior to enrollment.
• Active infection, including active hepatitis B \[defined as detectable HBV-DNA by local laboratory. Participants who are HBsAg positive or HBcAb positive at screening should have HBV-DNA tested\] and active hepatitis C \[defined as detectable HCV-RNA by local laboratory. Participants who are HCV antibody positive at screening should have HCV-RNA tested\].
• Any of the following cardiac-related criteria:
• Uncontrolled persistent (>4 weeks) hypertension (>140/90 mmHg).
• New York Heart Association (NYHA) Class (Appendix 11) III and IV heart disease, active ischemia, or other uncontrolled cardiac conditions such as angina.
• QTc interval Corrected QT interval using Fridericia's formula (QTcF) >=470 ms (based on 3 ECG results) or history of long QT syndrome.
• Resting ECG showing any clinically significant abnormalities in rhythm, conduction, or morphology (e.g., complete left bundle branch block, atrioventricular block third degree, atrioventricular block second degree, PR interval >250 ms).
• Left ventricular ejection fraction (LVEF) <50%.
• Any unresolved prior treatment toxicity greater than CTCAE Grade 1 at the start of study treatment, with the exception of alopecia, hemoglobin (see Inclusion Criterion #10), Grade 2 hypothyroidism stable on hormone replacement therapy, and Grade 2 pre-existing treatment-related neuropathy.
• Participants who have experienced a National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 Grade 3 or higher bleeding event within 4 weeks prior to enrollment.
• Participants who have experienced an arterial thrombotic or embolic event (e.g., cerebrovascular accident, including transient ischemic attack) within 6 months prior to enrollment, or a venous thrombotic event (including pulmonary embolism or deep vein thrombosis) within 3 months prior to enrollment.
• Participants who have experienced a seizure for any reason within 6 months prior to enrollment.
• Participants with known bleeding disorders or risk of intracranial hemorrhage (e.g., unexcised or unrepaired cerebral aneurysm, cerebrovascular malformation), or history of intracranial hemorrhage within 1 year prior to randomization.
• Participants with unhealed wounds, active ulceration, gastrointestinal perforation, or fracture within 3 months prior to enrollment.
• Participants with brain metastases.
• History of pancreatitis with prior tyrosine kinase inhibitors use, or current evidence of mild to moderate pancreatitis.
• Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulation, or significant bowel resection that may affect adequate absorption of NB003 and regorafenib.
• Any other clinically significant comorbidity, such as uncontrolled lung disorder, active infection, uncontrolled pericardial effusion, uncontrolled pleural effusion, or any other condition that, in the investigator's judgment, may affect protocol compliance, interfere with interpretation of study results, or increase participant safety risk.
• Participants judged by the investigator to be unwilling or unable (including incompetence) to comply with study procedures, restrictions, and requirements.
• Participants currently using (or unable to discontinue at least 2 weeks prior to enrollment) drugs or herbal supplements known to be strong inhibitors or inducers of CYP3A4, and other prohibited concomitant medications (Appendix 3).
• History of hypersensitivity to the active or inactive ingredients of NB003, regorafenib, or drugs with similar chemical structure or class to NB003 or regorafenib.