Phase 1/2 Study of HS-10375 in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

Inclusion criteria

• Men or women greater than or equal to 18 years.
• Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .
• Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II subjects.
• At least one measurable lesion in accordance with RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.
• Estimated life expectancy >12 weeks.
• Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Females must have the evidence of non-childbearing potential.
• Signed and dated Informed Consent Form.

Exclusion criteria

• Treatment with any of the following:

• Previous or current treatment with EGFR C797S inhibitors.
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10375.
• Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10375.
• Local radiotherapy for palliation within 2 weeks of the first dose of HS-10375, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10375.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10375.
• Inadequate bone marrow reserve or serious organ dysfunction.
• Uncontrolled pleural, ascites or pericardial effusion.
• Known and untreated, or active central nervous system metastases.
• Active autoimmune diseases or active infectious disease.
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications.
• History of hypersensitivity to any active or inactive ingredient of HS-10375 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10375.
• The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator.
• The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator.
• Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study.
• History of neuropathy or mental disorders, including epilepsy and dementia.