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

Official title

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）

Overview

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.

Interventions

• Drug HS-10504
  HS-10504 will be administered orally once daily in a continuous regimen. Participants will continue treatment until experiencing objective disease progression or meeting other protocol-specified criteria for discontinuation of study treatment.

Primary outcome measures

• the maximum tolerated dose (MTD) or the maximum applicable dose (MAD) [Time frame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (21 days).]

Secondary outcome measures (11)

• Incidence and severity of adverse events (AEs). [Time frame: From the first dose until 28 days after the last dose]
• maximum plasma concentration (Cmax) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Time frame: From the first dose until Circle 2 Day 1]
• Time to reach maximum plasma concentration (Tmax) for the first dose and multiple adminitration of HS-10504 (and its major matabolite) [Time frame: From the first dose until Circle 2 Day 1]
• half-life (T1/2) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Time frame: From the first dose until Circle 2 Day 1]
• Area under the curve (AUC) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504 [Time frame: From the first dose until Circle 2 Day 1]
• Trough plasma concentration (Ctrough) of HS-10504 (and its major matabolite) [Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months]
• Objective response rate (ORR) [Time frame: up to 24 months]
• Disease Control Rate (DCR) [Time frame: up to 24 months]
• Duration of response (DOR) [Time frame: up to 24 months]
• Progression-free survival (PFS) [Time frame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months]
• Overall survival (OS), only for dose-expansion stage subjects [Time frame: From the first dose up to death or withdrawal from study, whichever came first, assessed up to 24 months]

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:

• Prior or concurrent treatment with fourth-generation EGFR tyrosine kinase inhibitors.
• 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.
• 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
• Uncontrolled pleural effusion or ascites or pericardial effusion.
• Major surgery within 4 weeks before the first dose.
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The First Affiliated Hospital of Guangzhou Medical University — Guangzhou

Identifiers

NCT: NCT06461156 · HS-10504-101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗