A Study of HS-10342 in Patients With Advanced Solid Tumor

A Phase 1, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10342 in Patients With Advanced Solid Tumor

HS-10342 is a small molecular, oral potent, selective CDK4/6 inhibitor. The purpose of this study is to investigate the safety/tolerability and the pharmacokinetic profile of HS-10342 in Chinese advanced solid tumor patients. Preliminary efficacy will be also investigated in this study.

This is a phase 1, multicenter study to evaluate the safety, tolerability, pharmacokinetics and efficacy of HS-10342 in patients with advanced solid tumor by using a "3+3" dose escalation.

Inclusion Criteria:

• Subjects must meet all of the following inclusion criteria to be eligible for participation in this study:

  1. Pathologically confirmed solid tumor and failed from all standard treatment.

  2. At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.

  3. Eastern Cooperative Oncology Group (ECOG) performance status: 0-1.

  4. Life expectancy ≥ 3 months.

  5. Adequate function of major organs meets the following requirements:

     • Neutrophils ≥ 1.5×10^9/L
     • Platelets ≥ 90×10^9/L
     • Hemoglobin ≥ 90g/L
     • Total bilirubin≤ 1.5 × the upper limit of normal (ULN)
     • ALT and AST ≤ 2.5 × ULN
     • Cr ≤ 1.5 × ULN
     • Left ventricular ejection fraction (LVEF) ≥ 40%

  6. Good compliance of patient by physician's judgement.

  7. . Signed and dated informed consent.

Exclusion Criteria:

• Subjects who meet any of the following exclusion criteria are not to be enrolled in this study:

  1. Previously received therapy of anti-tumor agent targeting at CDK4/6.
  2. Less than 3 weeks from the last cell-toxicity chemotherapy, less than 6 weeks from last mitomycin or nitrosamine therapy
  3. Less than 3 weeks from any other anti-tumor therapy (including targets therapy, immunotherapy or other approved therapy)
  4. Less than 4 weeks from large area radiotherapy.
  5. Less than 7 days from any CYP3A4 strong inhibitor, strong inducer or a narrow window of medicine or food for CYP3A4 sensitive substrate.
  6. Having joined in other clinical trials within 4 weeks.
  7. Brain metastasis (well-controlled/well-treated brain metastasis by physician's judgement is allowed).
  8. Existing abnormal CTCAE≥grade 2 resulted from previous treatment(except grade 2 alopecia).
  9. Uncontrollable pleural effusion or ascites.
  10. Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug.
  11. History of serious allergy events or known being allergy constitution, or have a history of allergies to the drug components of this regimen.
  12. Patients with active infection.
  13. History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
  14. History of uncontrollable cardiac dysfunction, include(1)angina (2)clinical significant arrythmia or require drug intervention (3)myocardial infarction Less than 6 moths (4) other cardiac dysfunction (judged by the physician), such as any degree of heart block or QTc prolongation, QT interval corrected by Fridericia method(QTcF) >450 ms(men) or >470 ms(women); (5)any cardiac or nephric abnormal ≥ grade 2 found in screening.
  15. Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
  16. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
  17. History of neuropathy or dysphrenia, including epilepsy and dementia
  18. Determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment.