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

NCT ID: NCT05435248

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-02
• Study Completion Date: 2026-03-31

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.

Conditions

Advanced or Metastatic NSCLC

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

HS-10375

Intervention Type: DRUG

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

Interventions

HS-10375

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Li Zhang, Master

Role: CONTACT

zhangli@sysucc.org.cn

13902282893

Facility Contacts

Li Zhang

Role: primary

zhangli@sysucc.org.cn

13902282893

References

Zhan J, Xue J, Wu L, Zhang Z, Wang Q, Ma Y, Huang Y, Yang Y, Zhao Y, Fang W, Zhang Y, Liu Q, Xu W, Yang Y, Chen Z, Song B, Sun D, Sun X, Gao P, Zhao H, Zhang L. HS-10375, a selective EGFR C797S tyrosine kinase inhibitor, in advanced non-small cell lung cancer. J Transl Med. 2025 Jun 4;23(1):628. doi: 10.1186/s12967-025-06613-0.

Reference Type: DERIVED

PMID: 40468352 (View on PubMed)

Other Identifiers

HS-10375-101

Identifier Type: -

Identifier Source: org_study_id