A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors

Prior treatment

• Treatment with any of the following:
  • Previous or current treatment with other KRAS G12C inhibitors
  • Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of study treatment; Any investigational agents and large molecule antibodies within 28 days of the first dose of study treatment.
  • Local radiotherapy within 2 weeks prior to the first dose of study drug, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of study drug.
  • Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose
• Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy.
• Subjects with tumors known to harbor molecular alterations for which targeted therapy is locally approved, except for KRAS G12C.

Other illness

• History of other primary malignancies.
• Abnormal cardiac examination results.
• Severe, uncontrolled or active cardiovascular disorders.
• Diabetes ketoacidosis or hyperglycemia hyperosmolality
• Uncontrolled hypertension.
• Severe bleeding symptoms or bleeding tendencies.
• Severe arteriovenous thrombosis occurred
• Serious infection.
• Active infectious diseases.
• Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications
• Hepatic encephalopathy, hepatorenal syndrome, or ≥ Child Pugh B-grade cirrhosis.
• Interstitial lung disease (ILD).
• Serious neurological or mental disorders.
• Active autoimmune diseases

Other

• Active brain metastases.
• Patients with uncontrolled pleural, ascites or pericardial effusion
• Spinal cord compression
• Inadequate bone marrow reserve or organ functions.
• Continuous use of glucocorticoids

• Men or women greater than or equal to 18 years
• At least one measurable lesion in accordance with RECIST 1.1
• Must have an ECOG performance status of 0 or 1.
• Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
• Documentation of the presence of a KRAS G12C mutation
• Must provide tumor tissue sample
• No history of systemic anticancer therapy in metastatic/non-curable settings
• 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.
• Females must have the evidence of non-childbearing potential; Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Signed and dated Informed Consent Form.
• The subjects are able to comply with the process of the protocol.