Phase 1/2 Study of HS-10370 in Patients with Advanced Solid Tumors

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10370 Monotherapy in Patients with Advanced Solid Tumors

HS-10370 is an oral, highly selective, small molecular inhibitor of KRAS G12C. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10370 in Chinese advanced solid tumor patients.

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10370, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10370 in subjects with advanced solid tumors and evaluate the preliminary efficacy of HS-10370. Phase 2 will be conducted to evaluate the efficacy of HS-10370 in subjects with locally advanced or metastatic NSCLC with a KRAS G12C mutation.

Inclusion Criteria:

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

1. Men or women greater than or equal to 18 years
2. Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable
3. Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b 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:

   1. Previous or current treatment with KRAS G12C inhibitors
   2. Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370
   3. Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370
   4. Local radiotherapy for palliation within 2 weeks of the first dose of HS-10370, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10370
   5. Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370

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-10370 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10370

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