A Study of HS-10504 in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

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）

HS-10504 is a fourth-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR C797S mutation. This study will evaluate the safety, tolerability, pharmacokinetics and efficacy of HS-10504 in Chinese locally advanced or metastatic NSCLC.

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.