HS-10504 for advanced or metastatic non-small-cell lung cancer

A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10504 in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC）

This Phase 1 trial tests HS-10504, a fourth-generation EGFR inhibitor, in adults with advanced or metastatic EGFR-positive NSCLC who have progressed after prior EGFR-TKI therapy.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 230 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd. (Industry-sponsored)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Guangzhou)
• Trial ID: NCT06461156 on ClinicalTrials.gov

What this trial studies

HS-10504 is a fourth-generation EGFR tyrosine kinase inhibitor designed to target the EGFR C797S resistance mutation. This Phase 1, single-center study in China uses dose-escalation and possible expansion cohorts to characterize safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity. Eligible participants have histologically confirmed locally advanced or metastatic EGFR-positive NSCLC, measurable disease per RECIST 1.1, ECOG 0-1, and prior progression on EGFR-TKIs. Patients with other oncogenic drivers, histologic transformation, or prior fourth-generation EGFR inhibitors are excluded.

Who should consider this trial

Good fit: Adults (≥18) with locally advanced or metastatic EGFR-positive NSCLC, measurable disease, ECOG 0-1, life expectancy >12 weeks, and progression after prior EGFR-TKI therapy are the intended participants.

Not a fit: Patients whose tumors have alternative oncogenic drivers, transformed or mixed histology, prior fourth-generation EGFR inhibitor exposure, or poor performance status are unlikely to benefit from this drug.

Why it matters

Potential benefit: If successful, HS-10504 could provide a new targeted option for patients whose tumors have developed the EGFR C797S resistance mutation.

How similar studies have performed: Prior generations of EGFR inhibitors have been effective for other EGFR alterations, but agents specifically targeting C797S are novel and currently supported by limited early clinical data.

Eligibility criteria

Inclusion Criteria:

* Males or females, aged ≥ 18 years.
* Subjects with histologically or cytologically confirmed locally advanced or metastatic NSCLC
* Progressive disease on or after prior treatment with EGFR-TKIs.
* Enrollment will be restricted to participants with evidence of EGFR-positive in tumor as determined by local or central testing.
* At least 1 target lesion according to RECIST 1.1.
* ECOG PS score: 0-1.
* Estimated life expectancy\> 12 weeks.
* Men or women should be using adequate contraceptive measures throughout the study.
* Women must have the evidence of non-childbearing potential.
* Signed and dated Informed Consent Form.

Exclusion Criteria:

* Subjects with known oncogenic driver genes other than EGFR.
* Subjects with mixed cell histologic or with phenotypic transformation.
* Treatment with any of the following:

  1. Prior or concurrent treatment with fourth-generation EGFR tyrosine kinase inhibitors.
  2. Cytotoxic chemotherapy, any other investigational drugs, traditional Chinese medicine with anti-tumor indications, or other anti-tumor drugs within 14 days prior to the first dose of HS-10504 or require continued treatment with these drugs during the study.
  3. Any local radiotherapy 2 weeks prior to the first dose of study treatment; have received irradiation of more than 30% of bone marrow prior to the first dose
  4. Uncontrolled pleural effusion or ascites or pericardial effusion.
  5. Major surgery within 4 weeks before the first dose.
  6. CNS metastases with symptomatic or active progression.
* Subjects who have any grade ≥2 residual toxicities from prior therapies.
* Subjects who have history of other primary malignancies.
* Inadequate bone marrow reserve or hepatic and renal functions.
* Subjects with severe or poorly controlled diabetes, cardiovascular diseases or hypertension; subjects with severe arteriovenous thrombotic events, severe infection, clinically significant bleeding symptoms or clinically significant gastrointestinal dysfunction.
* Hypersensitivity to any ingredient of HS-10504.
* Moderate to severe pulmonary diseases.
* Prior history of significant neurological or mental disorders.
* Women who are breastfeeding or pregnant or planned to be pregnant during the study period.
* Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
* Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.

Where this trial is running

Guangzhou

• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou, China (Recruiting)

Study contacts

• Study coordinator: Jianxing He, PhD

Conditions Locally Advanced or Metastatic NSCLC; locally advanced or metastatic NSCLC; EGFR C797S; HS-10504