Overview

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.

Eligibility

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