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

Advanced or Metastatic NSCLC Clinical Trial

Official title:

A Phase 1/2, Open-label, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10375 Monotherapy in Patients With Advanced or Metastatic Non-Small-Cell Lung Cancer(NSCLC)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05435248
• Other study ID #: HS-10375-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: March 2, 2022
• Est. completion date: March 31, 2026

Study information

• Verified date: June 2022
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Li Zhang, Master
• Phone: 13902282893
• Email: zhangli[@]sysucc.org.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 354
• Est. completion date: March 31, 2026
• Est. primary completion date: March 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Men or women greater than or equal to 18 years.

2. Locally advanced or metastatic NSCLC patients confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable .

3. Pathological, NSCLC tissue samples can be used to test EGFR C797S mutation by central laboratory for Phase 1b and Phase II subjects.

4. At least one measurable lesion in accordance with RECIST 1.1.

5. Eastern Cooperative Oncology Group (ECOG) performance status: 0~1.

6. Estimated life expectancy >12 weeks.

7. 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.

8. Females must have the evidence of non-childbearing potential.

9. Signed and dated Informed Consent Form.

Exclusion Criteria:

1. 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.

2. Inadequate bone marrow reserve or serious organ dysfunction.

3. Uncontrolled pleural, ascites or pericardial effusion.

4. Known and untreated, or active central nervous system metastases.

5. Active autoimmune diseases or active infectious disease.

6. Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications.

7. 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.

8. The subject who is unlikely to comply with study procedures, restrictions, or requirements judged by the investigator.

9. The subject whose safety cannot be ensured or study assessments would be interfered judged by the investigator.

10. Pregnant women, breastfeeding women or woman who has a child-bearing plan during the study.

11. History of neuropathy or mental disorders, including epilepsy and dementia.

Related Conditions & MeSH terms

• Advanced or Metastatic NSCLC
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• HS-10375
HS-10375 will be administered orally once daily in a continuous regimen

Locations

Country	Name	City	State
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Jiangsu Hansoh Pharmaceutical Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the maximum tolerated dose (MTD)-Part Ia	Number of participants with dose limiting toxicity	From the single dose to the last dose of the first cycle defined as 21 days of multiple dosing (28 days)
Primary	To evaluate clinical activity/efficacy of HS-10375 by assessment of objective response rate-Part Ib/II	Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	Time Frame: up to 24 months
Secondary	Number of participants with treatment related adverse events	Number of participants with treatment related adverse events	From baseline until 28 days after the last dose
Secondary	Observed maximum plasma concentration (Cmax) after single dose of HS-10375	In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10375	From pre-dose to 120 hours after single dose on Day 1
Secondary	Time to reach maximum plasma concentration (Tmax) after single dose of HS-10375	In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10375	From pre-dose to 120 hours after single dose on Day 1
Secondary	Apparent terminal half-life (T1/2) after single dose of HS-10375	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 ?z	From pre-dose to 120 hours after single dose on Day 1
Secondary	Duration of response (DOR)	DOR assessed by RECIST 1.1 criteria	24 months
Secondary	Disease Control Rate (DCR)	DCR assessed by RECIST 1.1 criteria	24 months
Secondary	Progression-free survival (PFS)	PFS assessed by RECIST 1.1 criteria	24 months
Secondary	Overall survival (OS)		24 months