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

NCT05435248 | Recruiting Phase 1

• 1 other identifier: HS-10375-101
• Study Type: interventional
• Target: 354
• Locations: 1 country
• Sites: 1

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

Keywords

Advanced or metastatic NSCLC; EGFR C797S mutation; HS-10375

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (8)

• Number of participants with treatment related adverse events

  From baseline until 28 days after the last dose

• Observed maximum plasma concentration (Cmax) after single dose of HS-10375

  From pre-dose to 120 hours after single dose on Day 1

• 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

• Apparent terminal half-life (T1/2) after single dose of HS-10375

  From pre-dose to 120 hours after single dose on Day 1

• Duration of response (DOR)

  24 months

Study Arms (1)

HS-10375

EXPERIMENTAL

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.

Drug: HS-10375

Interventions

HS-10375 DRUG

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

HS-10375

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (1)

• 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.

  PMID: 40468352 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Li Zhang, Master

CONTACT

13902282893; zhangli@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2022
• First Posted: June 28, 2022
• Study Start: March 2, 2022
• Primary Completion: March 31, 2025
• Study Completion: March 31, 2026
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)