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

NCT07754123 | Not Yet Recruiting Phase 3 FDA Drug

• 1 other identifier: HS-10504-301
• Study Type: interventional
• Target: 206
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Advanced or Metastatic NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  Progression Free Survival (PFS) as assessed by Blinded independent Central Review (BICR) per RECIST 1.1

  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.

Secondary Outcomes (7)

• Overall Survival (OS)

  Start of study drug to Survival Endpoint through study completion, an average of 3 years.

• 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.

• 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.

• 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.

• 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.

Study Arms (2)

HS-10504 group

EXPERIMENTAL

Drug: HS-10504

Platinum-Based Doublet Chemotherapy Group

ACTIVE COMPARATOR

Drug: platinum-based doublet chemotherapy (Pemetrexed and Cisplatin/Carboplatin)

Interventions

HS-10504 DRUG

HS-10504 tablet

HS-10504 group

platinum-based doublet chemotherapy (Pemetrexed and Cisplatin/Carboplatin) DRUG

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.

Platinum-Based Doublet Chemotherapy Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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).
• History of other primary malignancies.
• Inadequate bone marrow reserve or hepatic/renal organ function.
• 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.
• Continuous systemic corticosteroid therapy (\>30 days) within 30 days prior to first dose, or requirement for long-term (≥30 days) corticosteroid use.
• 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.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2026
• First Posted: August 10, 2026
• Study Start (Estimated): September 17, 2026
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): July 31, 2031
• Last Updated: August 10, 2026

Record last verified: 2026-08