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

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10375 Monotherapy in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

HS-10375 is an oral, highly selective, small molecular inhibitor of EGFR C797S. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10375 in Chinese advanced or metastatic NSCLC.

Inclusion Criteria:

1. Men or women greater than or equal to 18 years.
2. Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .
3. Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II subjects.
4. At least one measurable lesion in accordance with RECIST 1.1.
5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.
6. Estimated life expectancy >12 weeks.
7. 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.
8. Females must have the evidence of non-childbearing potential.
9. Signed and dated Informed Consent Form.

Exclusion Criteria:

1. 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.

2. Inadequate bone marrow reserve or serious organ dysfunction.

3. Uncontrolled pleural, ascites or pericardial effusion.

4. Known and untreated, or active central nervous system metastases.

5. Active autoimmune diseases or active infectious disease.

6. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications.

7. 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.

8. The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator.

9. The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator.

10. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study.

11. History of neuropathy or mental disorders, including epilepsy and dementia.