Phase III Study of HS-10504 Versus Platinum-Based Doublet Chemotherapy in Patients With C797S+ NSCLC

Prior treatment

• Histological or phenotypic transformation (e.g., NSCLC to SCLC transformation, epithelial-to-mesenchymal transition) confirmed by tumor tissue obtained within 6 months prior to first dose.
• ≥ Grade 2 toxicities (per CTCAE v6.0) attributed to prior anti-tumor therapy (excluding alopecia and stable neurotoxicity).
• Continuous systemic corticosteroid therapy (\>30 days) within 30 days prior to first dose, or requirement for long-term (≥30 days) corticosteroid use.

Other illness

• History of other primary malignancies.
• Clinically significant cardiac abnormalities or severe/uncontrolled/active cardiovascular disease.
• Poorly controlled diabetes mellitus or hypertension.
• Significant clinical bleeding tendency or history of severe arterial/venous thromboembolic events.
• Severe or uncontrolled active infection.
• Active infectious diseases (e.g., active hepatitis B virus \[HBV\] infection).
• Clinically significant gastrointestinal disorders.
• Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B.
• Other pulmonary diseases that may interfere with assessment or management of drug-related pneumotoxicity.
• History of severe neurological or psychiatric disorders.

Other

• Presence of other well-documented driver gene mutations (e.g., ALK fusion, ROS1 fusion, KRAS activating mutations, MET exon 14 skipping, HER2 mutations, RET fusion).
• Inadequate bone marrow reserve or hepatic/renal organ function.

• Age ≥18 years.
• Histologically or cytologically confirmed locally advanced or metastatic NSCLC (Stage IIIB, IIIC, or IV).
• Documented failure after ≥1 prior line of EGFR TKI therapy with concurrent C797S mutation.
• At least one measurable target lesion per RECIST v1.1 criteria.