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

NCT05435274 | Unknown Phase 1

• 1 other identifier: HS-10376-101
• Study Type: interventional
• Target: 380
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Advanced Non-Small-Cell Lung Cancer

Keywords

NSCLC; Non-Small Cell Lung Cancer; HS-10376; EGFR/HER2 Exon 20 insertion mutation

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 (total 28 days)

• 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 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-10376

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

• Time to reach maximum plasma concentration (Tmax) after single dose of HS-10376

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

• Apparent terminal half-life (T1/2) after single dose of HS-10376

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

• Duration of response (DOR)

  24 months

Study Arms (1)

HS-10376

EXPERIMENTAL

Phase 1a：Dose Escalation：Subjects with advanced NSCLC will be enrolled in dose escalation cohorts. Dose escalation of HS-10376 will be done to determine maximum tolerated dose. Phase 1b：Dose Expansion：Depending on data obtained from the dose escalation part, dose expansion may proceed with multiple cohorts in subjects with advanced NSCLC having a EGFR/HER2 Exon 20 insertion mutation. Phase 2：Subjects with locally advanced or metastatic EGFR Exon 20 insertion NSCLC will be enrolled in phase 2 part to evaluate the efficacy and sufficient safety of HS-10376 as monotherapy.

Drug: HS-10376

Interventions

HS-10376 DRUG

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

HS-10376

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, tumor tissue samples can be used to test EGFR/HER2 Exon 20 insertion mutation by central laboratory for 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 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
• Inadequate bone marrow reserve or serious organ dysfunction
• Uncontrolled pleural, ascites or pericardial effusion
• Untreated, symptomatic or active central nervous system metastases
• Severe or poorly controlled hypertension
• Immunodeficiency disease and 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-10376 or to drugs with a similar chemical structure or drugs belonging to the same category of HS-10376
• 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

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300181, China

RECRUITING

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

Dingzhi Huang

CONTACT

18622221232; dingzhi72@163.com

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: September 30, 2021
• Primary Completion: October 7, 2024
• Study Completion: October 7, 2025
• Last Updated: June 28, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)