Phase I Study of HSK40118 in NSCLC Patients With EGFR Mutation

NCT ID: NCT06050980

Last Updated: 2023-09-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-27

Study Completion Date

2027-06-07

Brief Summary

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This is a phase I, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, PK and PD of HSK40118 when given orally in patients with active EGFR mutation locally advanced or metastatic non-small cell lung cancer (NSCLC).

The study will contain two phase: Phase Ia is dose escalation phase and Phase Ib is dose expansion phase.

Detailed Description

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Phase Ia will contain two part: Dose Escalation Part(Part A) and Extension Part(Part B). Part A based on the "3+3" design for dose escalation and safety evaluation requirements. Patient cohorts at selected doses may be extended to further investigate the tolerability, PK and PD of HSK40118. The number of patients to be enrolled will be up to 10 subjects in each Part B cohort. Approximately 30-70 subjects will be enrolled in Phase Ia.

Phase Ib no less than 130 subjects will be enrolled in each expansion cohort, cohort A will be enrolled 30-50 subjects, cohort B will be enrolled no less than 100 subjects.

Conditions

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NSCLC

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Phase Ia(Part A): HSK40118 as monotherapy

Phase 1a(Part A): dose escalation of HSK40118 as monotherapy at various dose levels

Group Type EXPERIMENTAL

HSK40118

Intervention Type DRUG

Oral administration, QD

Phase Ia(Part B): HSK40118 as monotherapy

Phase 1a(Part B): dose extention of HSK40118 as monotherapy at certain dose levels

Group Type EXPERIMENTAL

HSK40118

Intervention Type DRUG

Oral administration, QD

Phase Ib: HSK40118 as monotherapy

Phase 1b: dose expansion for HSK40118 as monotherapy at a dose determined during Phase 1 in patients with previous treatment with 3rd-generation EGFR-TKI

Group Type EXPERIMENTAL

HSK40118

Intervention Type DRUG

Oral administration, QD

Interventions

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HSK40118

Oral administration, QD

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age ≥ 18 years, Male and female patients, at time of signing informed consent form (ICF).
2. ECOG=0-1, with no deterioration in 2 weeks before first dose of HSK40118.
3. Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
4. Patients will provide blood or tumor sample according to their own willingness.
5. Patients in Phase Ia and Ib will fulfill the different criteria of the following:

Phase Ia(Part A): Previous treatment with at least one EGFR-TKI, including 1st, 2nd and 3rd-generation EGFR-TKI; Phase Ia(Part B)/Phase Ib: Previous treatment with 3rd-generation EGFR-TKI.
6. tumour lesions/lymph nodes: Phase Ia(Part A): Patients should have at least one assessable tumour lesions/malignant lymph nodes; Phase Ia(Part B) /Phase Ib: Patients should have at least one measurable tumour lesions/malignant lymph nodes.
7. Life expectancy ≥ 3 months.
8. Adequate hematologic and organ function per protocol.
9. Women of childbearing potential (WOCBP) and fertile males with WOCBP partners must use highly effective contraception per protocol throughout and after 90 days of the last dose of the study.

Exclusion Criteria

1. malignant tumor within 5 years, with the exception of cutaneous squamous cell carcinoma, cervical carcinoma in situ, papillary thyroid carcinoma, or other tumors with low malignancy.
2. Unstable spinal cord compression or brain metastases per protocol.
3. Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
4. Prior treatment with 4th-generation EGFR-TKIs(TKI for 3th-generation resistance).
5. Treatment with any of the following:

Prior treatment with an EGFR-TKI or other small-molecule anti-tumor drug within 7 days or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with chemotherapy, palliative radiotherapy, or Herbal therapy within 2 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter; Prior treatment with radiotherapy, immunotherapy/biotherapy therapy, or other pharmaceutical clinical trial within 4 weeks or approximately 5 × t1/2 prior to the first dose of HSK40118, whichever is shorter.
6. Treatment with inhibitors for P-glycoprotein (P-gp) within 7 days prior to the first dose of HSK40118.
7. Any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) grade 1 at the time of starting study treatment, with the exception of alopecia, dermal toxicity, and other toxicity considering no safety risks by investigator.
8. Any disease which would cause chronic diarrhea, eg. Crohn's disease, or irritable bowel syndrome.
9. Any disease which would preclude drug absorption, metabolism or pharmacokinetics, eg. active peptic ulcer or chronic gastroesophageal reflux disease.
10. Any severe disease of respiratory system, eg. interstitial lung disease, radiation pneumonitis, drug-induced pneumonitis, or uncontrolled asthma.
11. Patient who have clinically significant or uncontrolled cardiac disease, include: QTc interval ≥ 450(male)/470(female) msec; any clinically significant arrhythmia; left ventricular ejection fraction \< 50%; myocardial infarction, unstable angina, or class III/IV cardiac failure by the NYHA that occurred within 6 months prior to the first dose of HSK40118.
12. Any thromboembolic events within 6 months prior to the first dose of HSK40118; any familial or aquired thrombophilia.
13. Active bleeding at screening, history of visceral hemorrhage within 3 months prior to the first dose of HSK40118, or visceral bleeding tendency within 6 months prior to the first dose of HSK40118.
14. Patient who is undergoing, or receiving long-term(\> 6 months) anticoagulant/antiplatelet therapy; receiving drugs affecting coagulation function 1 week prior to the first dose of HSK40118.
15. INR, APTT \> 1.5xULN, or any bleeding tendency or coagulopathy at screening.
16. Uncontroled hypertension(systolic pressure ≥160mmHg, or diastolic pressure ≥100mmHg).
17. Any unstable systemic disease, eg. severe metabolic disease: liver cirrhosis, renal failure, or uremia.
18. Any disease of the eyes \> CTCAE v5.0 Grade 1.
19. Autologous transplantation surgery within 3 months prior to the first dose of HSK40118; Allogeneic transplantation, or stem-cell Transplant surgery within 6 months prior to the first dose of HSK40118; Major surgery or significant traumatic injury occurring within 4 weeks prior to the first dose of HSK40118.
20. Patients with HIV, HBV or HCV infection.
21. Patients with active syphilis infection.
22. Patients who have an uncontroled systematic infection, eg. fungal, bacterial, or virus infection.
23. Patients who would interfere with cooperation or outcome-assessment of the trial.
24. Allergic to any HSK40118 active constituent or ingredients.
25. (Child-bearing period women only)Patients testing positive for pregnancy, or during lactation.
26. Any other circumstances that would, in the investigator's judgment, prevent the subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Haisco Pharmaceutical Group Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, China

Site Status RECRUITING

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status RECRUITING

First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, China

Site Status RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, China

Site Status RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, China

Site Status RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Taizhou hospital of Zhejiang Province

Taizhou, Zhejiang, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Fangqiong Li

Role: CONTACT

+8602867258840

Facility Contacts

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Ning Li

Role: primary

010-87788713

Yongsheng Li

Role: primary

17784310187

Gen Lin

Role: primary

13313786157

Qitao Yu

Role: primary

13367816089

Yan Yu

Role: primary

13904505825

Zhiye Zhang

Role: primary

13783100985

Qiming Wang

Role: primary

13783590691

Lin Wu

Role: primary

13170419973

Xiujuan Qu

Role: primary

13604031355

Yuping Sun

Role: primary

13370582181

Caicun Zhou

Role: primary

13301825532

Dongqing Lv

Role: primary

13867622009

Other Identifiers

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HSK40118-101

Identifier Type: -

Identifier Source: org_study_id

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