Patient case: 58-year-old male with gastrointestinal stromal tumor; genetic feature: KIT (exon 9 502_503 duplication)

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

Summary: This study is a Multi-center, Open-label, single arm, Dose Escalation and Dose Extension Phase 1 Study to Determine the Maximum Tolerated Dose (MTD)/Recommend Phase 2 Dose (RP2D) and Evaluate PK/PD and preliminary Efficacy of HQP1351 in Patients With GIST or Other Solid Tumors.

Detailed description: The primary objective of this phase 1 study is to determine the maximum tolerated dose (MTD) / recommended phase 2 dose (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.

Eligibility: Inclusion Criteria:
  1. Male or not pregnant or lactating women, age≥18 years.
  2. Histologically or cytologically confirmed advanced/metastatic GISR or other solid tumors. Include:
  -  GIST patients failed at least one of the 3 TKIs includes imatinib, sunitinib, regorafenib GIST or intolerance to imatinib.
  -  Other solid tumors not suitable for standard treatment or have no effective treatment.
  3. ECOG≤ 2.
  4. Estimated survival at least 3 months.
  5. Adequate hematologic and bone marrow functions.
  6. Adequate renal and liver function.
  7. Heart function index:
  -  Troponin(I) ≤ Upper Limit of Normal;
  -  Ejection fraction >40%;
  -  QTc interval ≤ 450 ms in male or ≤ 470 ms in female.
  8. Negative serum pregnancy test (for women of childbearing potential) documented within the 24-hour prior to the first dose of investigational product.
  9. 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.
  10. 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).
  11. Willing and ability to comply with study procedures and follow-up examination.
  12. Willing to provide tumor samples (either archived tumor samples or fresh tumor biopsy ) for gene mutation detection.
  Exclusion Criteria:
  1. 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.
  2. Received any TKIs within 14 days before first dose of HQP1351.
  3. Attended any clinical trials on other drugs within 14 days before first dose of HQP1351.
  4. Have not recovered (> Grade 1 by CTCAE, v. 4.0) from AEs (except alopecia) due to agents previously administered.
  5. Malabsorption syndrome or other diseases that affect the absorption of oral drugs.
  6. Concurrent any significant or active cardiovascular disease, e.g. hypertension with SBP>140 mmHg and or DBP >90 mmHg, concurrent use any medication led to prolong QT interval.
  7. Pulmonary mean arterial pressure>25 mmHg by ECHO
  8. Significant severe cardiovascular conditions during previous TKI treatment.
  9. Uncontrollable hypertriglyceridemia.
  10. Performed major surgery (except for intravenous catheterization or bone marrow biopsy) within 14 days of first dose of HQP1351.
  11. 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.
  12. Brain metastasis.
  13. 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).
  14. 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.
  15. Subjects who are known to be allergic to pharmaceutical ingredients or their analogs.
  16. Pregnancy or lactation, or expect to be pregnant during the study period.
  17. 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.
  18. Any other condition or circumstance of that would, in the opinion of the investigator, make the patient unsuitable for participation in the study.

Relevance to patient case: not relevant