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

NB003-04 is a phase II/III, multicenter, open-label clinical study designed to evaluate the efficacy, safety, and pharmacokinetic (PK) profile of NB003 in patients with gastrointestinal stromal tumors aged 18 years and above (or the legal adult age of consent per local regulations, whichever is older). Participants who are eligible for this study are those who have experienced disease progression or documented intolerance following treatment with either imatinib and sunitinib or following treatment with imatinib. This study consists of two parts. Part 1 (hereinafter referred to as Part 1) compares the efficacy of NB003 versus regorafenib in patients who need a third-line therapy for GIST who have failed sequential therapy with imatinib and sunitinib. Part 2 (hereinafter referred to as Part 2) evaluates the efficacy of NB003 in patients who need a second-line therapy for GIST who have failed treatment with imatinib.

Inclusion Criteria: 1. Participants are \>=18 years of age (or the legal adult age as per local regulations, whichever is older) at the time of signing the ICF. 2. Participants, or legally authorized representatives permitted by local regulations, provide written informed consent for participation in the study. 3. Participants who have histologically confirmed locally advanced, unresectable, or metastatic GIST. 1. Part 1: Patients who have failed prior treatment with imatinib (including adjuvant therapy) and sunitinib for GIST due to disease progression or intolerance. Participants should also have no prior use of other TKI drugs. 2. Part 2: Patients who have failed prior treatment with imatinib (including adjuvant therapy) for GIST due to disease progression or intolerance. Participants should also have no prior use of other TKI drugs. 4. Participants with confirmed KIT gene mutation based on local or central laboratory molecular pathology reports. Mutation status must be determined using tissue-based PCR or DNA sequencing methods. The report should include results on the presence or absence of KIT exon 9/11/17 mutations for randomization stratification in Part 1 and efficacy-related analyses throughout the study. The molecular pathology report indicating KIT mutation status shall be submitted to the medical monitor for review during the screening period. If a local molecular pathology report is unavailable or provides insufficient information, archived tumor tissue samples or fresh biopsy samples must be provided for central laboratory confirmation of mutation status prior to enrollment. 5. Participants with at least one measurable lesion according to mRECIST. 6. Participants with an ECOG PS of 0 to 1. 7. Tumor sample requirement: Archival tumor samples in the form of formalin-fixed paraffin-embedded (FFPE) tissue sections or FFPE blocks obtained prior to enrollment, or tissue samples from a tumor biopsy (excisional, core needle, or fine-needle aspiration). 8. Participants with an expected life expectancy of \>=12 weeks. 9. Participants shall have adequate organ and bone marrow function. Transfusions and/or treatment with erythropoietin and/or granulocyte colony stimulating factor/granulocyte macrophage colony stimulating factor (G-CSF/GM-CSF) are not permitted within 14 days prior to the screening laboratory blood draw under any circumstances. The criteria are defined as follows: * Hemoglobin \>=9 g/dL (5.59 mmol/L). * Absolute neutrophil count (ANC) \>=1.5 x 10\^9/L (1500/mm\^3). * Platelet count \>=100 x 10\^9/L (100,000/mm\^3). * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \=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) \