Phase 1/2 Study of HS-10375 in Patients with Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

Phase 1

Recruiting

Conditions: Advanced or Metastatic NSCLC

Interventions: Drug: HS-10375

Registration Number: NCT05435248

Lead Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Brief Summary: HS-10375 is an oral, highly selective, small molecular inhibitor of EGFR C797S. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10375 in Chinese advanced or metastatic NSCLC.

Detailed Description: Not available

Recruitment & Eligibility

Status: RECRUITING

Sex: All

Target Recruitment: 354

Inclusion Criteria

Men or women greater than or equal to 18 years.
Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .
Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II subjects.
At least one measurable lesion in accordance with RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.
Estimated life expectancy >12 weeks.
Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
Females must have the evidence of non-childbearing potential.
Signed and dated Informed Consent Form.

Exclusion Criteria

Treatment with any of the following:
- Previous or current treatment with EGFR C797S inhibitors.
- Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10375.
- Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10375.
- Local radiotherapy for palliation within 2 weeks of the first dose of HS-10375, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10375.
- Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10375.
Inadequate bone marrow reserve or serious organ dysfunction.
Uncontrolled pleural, ascites or pericardial effusion.
Known and untreated, or active central nervous system metastases.
Active autoimmune diseases or active infectious disease.
Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications.
History of hypersensitivity to any active or inactive ingredient of HS-10375 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10375.
The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator.
The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator.
Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study.
History of neuropathy or mental disorders, including epilepsy and dementia.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HS-10375	HS-10375	Experimental: HS-10375（Phase 1a：Dose Escalation） Subjects with advanced or metastatic NSCLC will be enrolled in dose escalation cohorts. Dose escalation of HS-10375 will be done to determine maximum tolerated dose. Experimental: HS-10375（Phase 1b：Dose Expansion） Depending on data obtained from the dose escalation part, dose expansion may proceed with multiple cohorts in subjects with advanced or metastatic NSCLC having a EGFR C797S mutation. Experimental: HS-10375（Phase 2） Subjects with locally advanced or metastatic EGFR C797S mutant NSCLC will be enrolled in phase 2 part to evaluate the efficacy and sufficient safety of HS-10375 as monotherapy.

Primary Outcome Measures

Name	Time	Method
To determine the maximum tolerated dose (MTD)-Part Ia	From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days)	Number of participants with dose limiting toxicity
To evaluate clinical activity/efficacy of HS-10375 by assessment of objective response rate-Part Ib/II	Time Frame: up to 24 months	Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)

Secondary Outcome Measures

Name	Time	Method
Observed maximum plasma concentration (Cmax) after single dose of HS-10375	From pre-dose to 120 hours after single dose on Day 1	In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10375
Time to reach maximum plasma concentration (Tmax) after single dose of HS-10375	From pre-dose to 120 hours after single dose on Day 1	In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10375
Disease Control Rate (DCR)	24 months	DCR assessed by RECIST 1.1 criteria
Progression-free survival (PFS)	24 months	PFS assessed by RECIST 1.1 criteria
Number of participants with treatment related adverse events	From baseline until 28 days after the last dose	Number of participants with treatment related adverse events
Duration of response (DOR)	24 months	DOR assessed by RECIST 1.1 criteria
Overall survival (OS)	24 months
Apparent terminal half-life (T1/2) after single dose of HS-10375	From pre-dose to 120 hours after single dose on Day 1	Apparent terminal half-life is the time measured for the concentration to decrease by one half. Terminal half-life calculated by natural log 2 divided by λz

Trial Locations

Locations (1): Sun Yat-sen University Cancer Center
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Guangzhou, Guangdong, China