Phase 1/2 Study of HS-10376 in Patients With Non-Small Cell Lung Cancer

Advanced Non-Small-Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of HS-10376 Monotherapy in Patients With Advanced Non-small-Cell Lung Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05435274
• Other study ID #: HS-10376-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: September 30, 2021
• Est. completion date: October 7, 2025

Study information

• Verified date: June 2022
• Source: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Contact: Dingzhi Huang
• Phone: 18622221232
• Email: dingzhi72[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

HS-10376 is an oral, highly selective, small molecular inhibitor of EGFR/HER2 Exon 20 insertion mutation. This study will evaluate the safety, tolerability, pharmacokinetics and clinical activity of HS-10376 in Chinese advanced Non-Small Cell Lung Cancer (NSCLC) patients.

Description:

This is a phase 1/2, first-in-human, open-label, multicenter study of HS-10376, this study has two parts: phase 1 and phase 2. The phase 1 portion consists of dose escalation and dose expansion, which is aimed to assess the safety and tolerability of HS-10376 in subjects with advanced NSCLC and evaluate the preliminary efficacy of HS-10376. Phase 2 will be conducted to evaluate the efficacy of HS-10376 in subjects with locally advanced or metastatic NSCLC with a EGFR Exon 20 insertion mutation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 380
• Est. completion date: October 7, 2025
• Est. primary completion date: October 7, 2024
• 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, tumor tissue samples can be used to test EGFR/HER2 Exon 20 insertion mutation by central laboratory for 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 Exon 20 insertion inhibitors, HER2 Exon 20 insertion inhibitors or EGFR/HER2 Exon 20 insertion inhibitors
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of HS-10376
• Any investigational agents and large molecule antibodies within 28 days of the first dose of HS-10376
• Local radiotherapy for palliation within 2 weeks of the first dose of HS-10376, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks of the first dose of HS-10376
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose of HS-10376

2. Inadequate bone marrow reserve or serious organ dysfunction

3. Uncontrolled pleural, ascites or pericardial effusion

4. Untreated, symptomatic or active central nervous system metastases

5. Severe or poorly controlled hypertension

6. Immunodeficiency disease and active infectious disease

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

8. History of hypersensitivity to any active or inactive ingredient of HS-10376 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10376

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

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

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

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

Related Conditions & MeSH terms

• Advanced Non-Small-Cell Lung Cancer
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms

Intervention

Drug:
• HS-10376
HS-10376 will be administered orally once daily in a continuous regimen

Locations

Country	Name	City	State
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin

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 (total 28 days)
Primary	To evaluate clinical activity/efficacy of HS-10376 by assessment of objective response rate-Phase Ib/II	Objective response rate (ORR) assessed by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)	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-10376	In the study of single-dose, Cmax will be obtained following administration of a single oral dose of HS-10376	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-10376	In the study of single-dose, Tmax will be obtained following administration of a single oral dose of HS-10376	From pre-dose to 120 hours after single dose on Day 1
Secondary	Apparent terminal half-life (T1/2) after single dose of HS-10376	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