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

Inclusion Criteria:

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

Exclusion Criteria:

1. 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).
2. 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.
3. ≥ Grade 2 toxicities (per CTCAE v6.0) attributed to prior anti-tumor therapy (excluding alopecia and stable neurotoxicity).
4. History of other primary malignancies.
5. Inadequate bone marrow reserve or hepatic/renal organ function.
6. Clinically significant cardiac abnormalities or severe/uncontrolled/active cardiovascular disease.
7. Poorly controlled diabetes mellitus or hypertension.
8. Significant clinical bleeding tendency or history of severe arterial/venous thromboembolic events.
9. Severe or uncontrolled active infection.
10. Continuous systemic corticosteroid therapy (\>30 days) within 30 days prior to first dose, or requirement for long-term (≥30 days) corticosteroid use.
11. Active infectious diseases (e.g., active hepatitis B virus \[HBV\] infection).
12. Clinically significant gastrointestinal disorders.
13. Hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B.
14. Other pulmonary diseases that may interfere with assessment or management of drug-related pneumotoxicity.
15. History of severe neurological or psychiatric disorders.