A Study of HQP1351 in Patients With GIST or Other Solid Tumors

The primary objective of this phase 1 study is to determine the RP2D of HQP1351 in patients with GIST or other solid tumors. The secondary objective is to assess the safety, tolerability, PK and preliminary anti-tumor activities of HQP1351 in Patients With GIST or Other Solid Tumors.

Inclusion criteria

• Male or not pregnant or lactating women, age≥12years.
• Advanced and/or metastatic GIST or other solid tumors, confirmed by histology and/or cytology. GIST patients must be primary resistant to imatinib (tumor progresses within 6 months first-line imatinib treatment, or succinate dehydrogenase B (SDHB) deficient confirmed by immunohistochemistry, or NF1 mutation), OR imatinib or imatinib and at least one other TKI treatment failure (after imatinib or other TKI treatment for more than 6 months, tumor progress again after achieving tumor remission or stability).
• ECOG≤ 2.
• Estimated survival at least 3 months.
• Adequate hematologic and bone marrow functions.
• Adequate renal and liver function.
• Heart function index:

• Troponin(I/T) ≤ Upper Limit of Normal;
• Ejection fraction >40%;
• QTc interval ≤ 450 ms in male or ≤ 470 ms in female.
• Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour prior to the first dose of investigational product.
• Willing to use contraception by a method that is deemed effective by the investigator by Subject and their partners throughout the treatment period and for at least 30 days following the last dose of study drug.
• Ability to understand and willingness to sign a written informed consent form (the consent form must be signed by the subject prior to any study-specific procedures).
• Willing and ability to comply with study procedures and follow-up examination.

Exclusion criteria

• Received any anti-cancer chemotherapy, biological agent treatment (e.g. Monoclonal antibody), immunotherapy (e.g. IFN) or radiotherapy with 28 days or 5 times half- time before first dose of HQP1351.
• Received any TKIs within 14 days before first dose of HQP1351.
• Attended any clinical trials on other drugs within 14 days before first dose of HQP1351.
• Have not recovered (> Grade 1 by CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
• Malabsorption syndrome or other diseases that affect the absorption of oral drugs.
• Cardiovascular diseases of clinical significance, uncontrollable or active, including but not limited to: history of myocardial infarction; unstable history of angina pectoris; a history of congestive heart failure or lower left ventricular ejection fraction (LVEF) than normal limit within 6 months; the history of atrial arrhythmias was judged by the researchers to have important clinical significance; history of ventricular arrhythmias, etc.
• Hypertension was still poorly controlled after medication treatment (SBP > 140 mmHg and/or DBP > 90 mmHg).
• Concurrent use any medication led to prolong QT interval.
• Pulmonary mean arterial pressure>35 mmHg by ECHO.
• Significant severe cardiovascular conditions during previous TKI treatment.
• Uncontrollable hypertriglyceridemia.
• Performed major surgery (except for intravenous catheterization or bone marrow biopsy) within 14 days of first dose of HQP1351.
• Arterial thrombosis or embolism events such as cerebrovascular accident (including transient ischemic attack, TIA), or venous thrombosis events or pulmonary embolism within 6 months before the first dose of HQP1351 or deep vein thrombosis within 3 months before the first dose of HQP1351.
• Brain metastasis.
• Had other primary malignant tumors in the last three years (exception of the tumors being cured for 5 years or more, or complete removal of non-melanoma skin cancer or successful treatment of carcinoma in situ, or the controlled prostate cancer).
• Had active, symptomatic infections (including known infections of HIV, viral hepatitis (A, B, or C)). If there is no history of infection, screening is not required.
• Subjects who are known to be allergic to pharmaceutical ingredients or their analogs.
• Pregnancy or lactation, or expect to be pregnant during the study period.
• According to the judgment of the investigator or sponsor, any symptoms or disease of the subject may jeopardize the safety or safety assessment of the subject.
• Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.