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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Non-Small-Cell Lung Cancer
• Intervention / Treatment: Drug: HS-10376

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 380
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Dingzhi Huang; Phone Number: 18622221232; Email: dingzhi72@163.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300181
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Dingzhi Huang; Phone Number: 18622221232; Email: dingzhi72@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SEQUENTIAL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response (DOR)	DOR assessed by RECIST 1.1 criteria	24 months
Disease Control Rate (DCR)	DCR assessed by RECIST 1.1 criteria	24 months
Progression-free survival (PFS)	PFS assessed by RECIST 1.1 criteria	24 months
Overall survival (OS)		24 months
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
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
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
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 λz.	From pre-dose to 120 hours after single dose on Day 1

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 30, 2021
• Primary Completion (ANTICIPATED): October 7, 2024
• Study Completion (ANTICIPATED): October 7, 2025

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 27, 2022
• First Posted (ACTUAL): June 28, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 28, 2022
• Last Update Submitted That Met QC Criteria: June 27, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: NSCLC; Non-Small Cell Lung Cancer; HS-10376; EGFR/HER2 Exon 20 insertion mutation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: HS-10376-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No