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

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:

• Men or women greater than or equal to 18 years
• Locally advanced or metastatic cancer patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable
• Pathological, tumor tissue samples can be used to test KRAS G12C mutation by central laboratory for Phase 1b 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 KRAS G12C inhibitors
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10370
• Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10370
• 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
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10370
• 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-10370 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10370
• 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