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

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:

• Pathologically confirmed solid tumor and failed from all standard treatment.
• At least one extracranial measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0-1.
• Life expectancy ≥ 3 months.
• 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%
• Good compliance of patient by physician's judgement.
• . Signed and dated informed consent.

Exclusion criteria

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

• Previously received therapy of anti-tumor agent targeting at CDK4/6.
• Less than 3 weeks from the last cell-toxicity chemotherapy, less than 6 weeks from last mitomycin or nitrosamine therapy
• Less than 3 weeks from any other anti-tumor therapy (including targets therapy, immunotherapy or other approved therapy)
• Less than 4 weeks from large area radiotherapy.
• Less than 7 days from any CYP3A4 strong inhibitor, strong inducer or a narrow window of medicine or food for CYP3A4 sensitive substrate.
• Having joined in other clinical trials within 4 weeks.
• Brain metastasis (well-controlled/well-treated brain metastasis by physician's judgement is allowed).
• Existing abnormal CTCAE≥grade 2 resulted from previous treatment(except grade 2 alopecia).
• Uncontrollable pleural effusion or ascites.
• Inability to swallow, intestinal obstruction or other factors affecting the administration and absorption of the drug.
• History of serious allergy events or known being allergy constitution, or have a history of allergies to the drug components of this regimen.
• Patients with active infection.
• History of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disease, history of organ transplantation.
• 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.
• Males and females of reproductive potential who are unwilling to use an "effective", protocol specified method(s) of contraception during the study.
• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study.
• History of neuropathy or dysphrenia, including epilepsy and dementia
• Determined by the physician, any coexisting disease might lead to life threatening complications or avoid the patients from accomplishing the treatment.