Clinical trial NCT06461156: 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）
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Locally Advanced or Metastatic NSCLC
Keywords: locally advanced or metastatic NSCLC
EGFR C797S
HS-10504
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-14
Enrollment: 230
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


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.

Primary outcomes:
measure: the maximum tolerated dose (MTD) or the maximum applicable dose (MAD)
timeFrame: From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (21 days).
Secondary outcomes:
measure: Incidence and severity of adverse events (AEs).
timeFrame: From the first dose until 28 days after the last dose
measure: maximum plasma concentration (Cmax) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504
timeFrame: From the first dose until Circle 2 Day 1
measure: Time to reach maximum plasma concentration (Tmax) for the first dose and multiple adminitration of HS-10504 (and its major matabolite)
timeFrame: From the first dose until Circle 2 Day 1
measure: half-life (T1/2) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504
timeFrame: From the first dose until Circle 2 Day 1
measure: Area under the curve (AUC) of HS-10504 (and its major matabolite) for the first dose and multiple dose adminitration of HS-10504
timeFrame: From the first dose until Circle 2 Day 1
measure: Trough plasma concentration (Ctrough) of HS-10504 (and its major matabolite)
timeFrame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months
measure: Objective response rate (ORR)
timeFrame: up to 24 months
measure: Disease Control Rate (DCR)
timeFrame: up to 24 months
measure: Duration of response (DOR)
timeFrame: up to 24 months
measure: Progression-free survival (PFS)
timeFrame: From the first dose to disease progression or withdrawal from study, whichever came first, assessed up to 24 months
measure: Overall survival (OS), only for dose-expansion stage subjects
timeFrame: From the first dose up to death or withdrawal from study, whichever came first, assessed up to 24 months
Other outcomes:
Locations:
Study officials:
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