Phase I Study of HSK40118 in NSCLC Patients With EGFR Mutation

NCT06050980 | Recruiting Phase 1

• 1 other identifier: HSK40118-101
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (4)

• MTD

  MTD determination: dose limiting toxicity (DLT) rate

  Up to approximately 52 months

• DLTs

  Incidence of dose-limiting toxicities (DLTs) at Cycle 0 and Cycle1

  Up to approximately 52 months

• AEs

  Rate and severity of adverse events of HSK40118 as monotherapy

  Up to approximately 52 months

• Eastern Cooperative Oncology Group Performance Status Scale(ECOG PS)

  Change of the grade as a part of HSK40118 safety data. The functional status of patients will be assessed by the ECOG PS, which is described as a scale including grade 0(fully active) to grade 5(dead).

  Up to approximately 52 months

Secondary Outcomes (15)

• Overall response rate(ORR)

  Up to approximately 52 months

• Disease control rate (DCR)

  Up to approximately 52 months

• Duration of response (DOR)

  Up to approximately 52 months

• Progression free survival (PFS)

  Up to approximately 52 months

• Overall survival (OS)

  Up to approximately 52 months

Other Outcomes (2)

• EGFR protein degradation

  Tissue samples will be collected on 2 occasions for each patient throughout study: screening period, cycle 1 day 15(±7 days).

• circulation tumor DNA(ctDNA)

  Blood samples will be collected on 3 occasions for each patient throughout study: screening period, cycle 2 day 1, cycle 3 day 1.

Study Arms (3)

Phase Ia(Part A): HSK40118 as monotherapy

EXPERIMENTAL

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

Drug: HSK40118

Phase Ia(Part B): HSK40118 as monotherapy

EXPERIMENTAL

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

Drug: HSK40118

Phase Ib: HSK40118 as monotherapy

EXPERIMENTAL

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

Drug: HSK40118

Interventions

HSK40118 DRUG

Oral administration, QD

Phase Ia(Part A): HSK40118 as monotherapy; Phase Ia(Part B): HSK40118 as monotherapy; Phase Ib: HSK40118 as monotherapy

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, Male and female patients, at time of signing informed consent form (ICF).
• ECOG=0-1, with no deterioration in 2 weeks before first dose of HSK40118.
• Histological or cytological confirmed diagnosis of unresectable locally advanced or metastatic NSCLC.
• Patients will provide blood or tumor sample according to their own willingness.
• 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.
• 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.
• Life expectancy ≥ 3 months.
• Adequate hematologic and organ function per protocol.
• 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.

You may not qualify if:

• 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.
• Unstable spinal cord compression or brain metastases per protocol.
• Uncontrollable pleural effusion, ascites, or pericardial effusion per protocol.
• Prior treatment with 4th-generation EGFR-TKIs(TKI for 3th-generation resistance).
• 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.
• Treatment with inhibitors for P-glycoprotein (P-gp) within 7 days prior to the first dose of HSK40118.
• 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.
• Any disease which would cause chronic diarrhea, eg. Crohn's disease, or irritable bowel syndrome.
• Any disease which would preclude drug absorption, metabolism or pharmacokinetics, eg. active peptic ulcer or chronic gastroesophageal reflux disease.
• Any severe disease of respiratory system, eg. interstitial lung disease, radiation pneumonitis, drug-induced pneumonitis, or uncontrolled asthma.
• 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.
• Any thromboembolic events within 6 months prior to the first dose of HSK40118; any familial or aquired thrombophilia.
• 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.
• 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.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (12)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, Beijing Municipality, 100021, China

RECRUITING

Chongqing Cancer Hospital

Chongqing, Chongqing Municipality, 400000, China

RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, 350000, China

RECRUITING

Guangxi Medical University Cancer Hospital

Nanning, Guangxi, 530000, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

RECRUITING

First Affiliated Hospital of Henan University of Science and Technology

Luoyang, Henan, 471000, China

RECRUITING

Henan Cancer Hospital

Zhengzhou, Henan, 450000, China

RECRUITING

Hunan Cancer Hospital

Changsha, Hunan, 410031, China

RECRUITING

The First Hospital of China Medical University

Shenyang, Liaoning, 110002, China

RECRUITING

Shandong Cancer Hospital

Jinan, Shandong, 250117, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Taizhou hospital of Zhejiang Province

Taizhou, Zhejiang, 318050, China

RECRUITING

Central Study Contacts

Fangqiong Li

CONTACT

+8602867258840; lifangq@haisco.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2023
• First Posted: September 22, 2023
• Study Start: March 27, 2023
• Primary Completion: August 30, 2025
• Study Completion (Estimated): June 7, 2027
• Last Updated: September 22, 2023

Record last verified: 2023-09

Locations

CN (12)