Advanced or Metastatic NSCLC
Conditions
Brief summary
This is a randomized, controlled, open-label, multicenter Phase III clinical study designed to evaluate the efficacy and safety of oral HS-10504 monotherapy versus platinum-based doublet chemotherapy in participants with locally advanced or metastatic NSCLC harboring EGFR C797S mutation after failure of EGFR TKI therapy.
Interventions
DRUGHS-10504
HS-10504 tablet
DRUGplatinum-based doublet chemotherapy (Pemetrexed and Cisplatin/Carboplatin)
Participants will receive 4 cycles of standard platinum-based doublet chemotherapy (selected by the investigator based on participant's condition and tolerance): * Option 1: Pemetrexed 500 mg/m² IV infusion + Cisplatin 75 mg/m² IV infusion on Day 1 of each 21-day cycle. * Option 2: Pemetrexed 500 mg/m² IV infusion + Carboplatin AUC 5 IV infusion on Day 1 of each 21-day cycle. * Substitution Rule: Cisplatin and carboplatin may be substituted if intolerable due to safety, while maintaining 4 total cycles of platinum-based therapy.
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | Progression Free Survival (PFS) as assessed by Blinded independent Central Review (BICR) per RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Start of study drug to Survival Endpoint through study completion, an average of 3 years. | Overall survival (OS) |
| PFS | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | PFS assessed by Investigator assessment per RECIST 1.1 |
| ORR | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | Confirmed ORR by BICR and Investigator per RECIST 1.1 |
| DoR | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | DoR by BICR and Investigator per RECIST 1.1 |
| DCR | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | DCR by BICR and Investigator per RECIST 1.1 |
| AE | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | AE assessed by investigators. |
| SAE | From baseline, then every 6 weeks, until disease progression or discontinuation from study. From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. | SAE assessed by investigators. |
Outcome results
None listed