Clinical Trial of YH25448 in Patients with EGFR Mutation Positive Advanced NSCLC

NCT03046992 | Completed Phase 1 DMC

• 1 other identifier: YH25448-201
• Study Type: interventional
• Target: 224
• Locations: 1 country
• Sites: 16

Brief Summary

YH25448 is an oral, highly potent, mutant-selective and irreversible EGFR Tyrosine-kinase inhibitors (TKIs) targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. YH25448 is expected to beneficial for the NSCLC patients with brain metastasis due to good blood brain barrier (BBB) penetration property as well as for the treatment of primary lung lesion and extracranial lesions. This study will be conducted to evaluate the safety, tolerability and efficacy of YH25448 in locally advanced or metastatic NSCLC patients with EGFR mutations.

Conditions

EGFR Gene Mutation

Keywords

EGFR; Non-Small Cell Lung Cancer; T790M; Brain Metastasis

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability by Common Terminology Criteria for Adverse Events (CTCAE) v4.03

  To assess the safety and tolerability profile of YH25448 by Common Terminology Criteria for Adverse Events (CTCAE) v4.03; vital signs (blood pressure, pulse, weight); laboratory parameters (clinical chemistry, hematology, urinalysis); physical examination; centrally reviewed electrocardiograms (ECGs), echocardiogram or multiple gated acquisition scan and performance status.

  Safety and tolerability profile will be collected from baseline until 28 days after the last dose, expected average 1 year.

• Objective Response Rate (ORR)

  Per Response Evaluation Criteria in Solid Tumours (RECIST version 1.1) assessed by MRI or CT. ORR is the percentage of patients with at least 1 visit response of Complete Response (CR) or Partial Response (PR) (according to independent review), prior to progression or further anti-cancer therapy.

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

Secondary Outcomes (8)

• Duration of Response (DoR)

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

• Disease Control Rate (DCR)

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

• Progression-Free Survival (PFS)

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

• Overall Survival (OS)

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

• Tumor shrinkage

  At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.

Study Arms (1)

YH25448

EXPERIMENTAL

* Dose Escalation Phase: Consists of 7 Cohorts * Dose Expansion Phase: Consists of 5 Cohorts * Dose Extension Phase: Consists of 2 Cohorts

Drug: YH25448

Interventions

YH25448 DRUG

* Dose Escalation: YH25448 20mg\~320mg, PO * Dose Expansion: YH25448 40mg\~240mg, PO * Dose Extension: Recommended Dose 240mg of YH25448

YH25448

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of NSCLC with single activating EGFR mutations.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months.
• At least one measurable extracranial lesion, not previously irradiated and not chosen biopsy during the study screening period.
• Prior to enrolling in the study, patients must have central confirmation of T790M+ mutation status from a sample taken after documented progression on the EGFR-TKIs therapy according to cohort.

You may not qualify if:

• Spinal cord compression.
• Brain metastases with symptomatic and/or requiring steroid for at least 2 weeks prior to start of study treatment.
• Known intracranial hemorrhage which is unrelated to tumor.
• Central Nervous System (CNS) complications that require urgent neurosurgical intervention (e.g. resection or shunt placement).
• Leptomeningeal metastasis prior to study treatment.
• Past medical history of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
• Any cardiovascular disease as followed.
• History of symptomatic congestive heart failure (CHF) or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction or unstable angina within 6 months of the first dose of study treatment
• Left ventricular ejection fraction (LVEF) \< 50%

Sponsors & Collaborators

• Yuhan Corporation: lead

Study Sites (16)

The Catholic University of Korea, Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-do, 14647, South Korea

Location

National Cancer Center

Goyang-si, Gyeonggi-do, 03080, South Korea

Location

CHA Bundang Medical Center, CHA University

Seongnam-si, Gyeonggi-do, 13496, South Korea

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

The Catholic University of Korea, St. Vincent's Hospital

Suwon, Gyeonggi-do, 16247, South Korea

Location

Gyeongsang National University Hospital

Jinju, Gyeongsangnam-do, 52727, South Korea

Location

Chungbuk National University Hospital

Cheongju-si, North Chungcheong, 28644, South Korea

Location

Inje University Haeundae Paik Hospital

Busan, 48108, South Korea

Location

Gachon University Gil Medical Center

Incheon, 21565, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Kangbuk Samsung Hospital

Seoul, 03181, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

SMG-SNU Boramae Medical Center

Seoul, 07061, South Korea

Location

Severance Hospital

Seoul, South Korea

Location

Ulsan University Hospital

Ulsan, 44033, South Korea

Location

Related Publications (5)

• Han JY, Ahn MJ, Lee KH, Lee YG, Kim DW, Min YJ, Kim SW, Cho EK, Kim JH, Lee GW, Lee SS, Lee NM, Jang HW, Han H, Park H, Lee J, Cho BC. Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study. BMC Med. 2024 Oct 8;22(1):428. doi: 10.1186/s12916-024-03620-8.

  PMID: 39379931 DERIVED

• Kim B, Lee J, Jang H, Lee N, Mehta J, Jang SB. Effects of Acid-Reducing Agents on the Pharmacokinetics of Lazertinib in Patients with EGFR Mutation-Positive Advanced Non-Small-Cell Lung Cancer. Adv Ther. 2022 Oct;39(10):4757-4771. doi: 10.1007/s12325-022-02286-z. Epub 2022 Aug 13.

  PMID: 35962934 DERIVED

• Cho BC, Han JY, Kim SW, Lee KH, Cho EK, Lee YG, Kim DW, Kim JH, Lee GW, Lee JS, Shim BY, Kim JS, Chun SH, Lee SS, Kim HR, Hong MH, Ahn JS, Sun JM, Lee Y, Lee DH, Kang JA, Lee N, Kwon MJ, Espenschied C, Yablonovitch A, Ahn MJ. A Phase 1/2 Study of Lazertinib 240 mg in Patients With Advanced EGFR T790M-Positive NSCLC After Previous EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol. 2022 Apr;17(4):558-567. doi: 10.1016/j.jtho.2021.11.025. Epub 2021 Dec 24.

  PMID: 34958928 DERIVED

• Ahn MJ, Han JY, Lee KH, Kim SW, Kim DW, Lee YG, Cho EK, Kim JH, Lee GW, Lee JS, Min YJ, Kim JS, Lee SS, Kim HR, Hong MH, Ahn JS, Sun JM, Kim HT, Lee DH, Kim S, Cho BC. Lazertinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: results from the dose escalation and dose expansion parts of a first-in-human, open-label, multicentre, phase 1-2 study. Lancet Oncol. 2019 Dec;20(12):1681-1690. doi: 10.1016/S1470-2045(19)30504-2. Epub 2019 Oct 3.

  PMID: 31587882 DERIVED

• Yun J, Hong MH, Kim SY, Park CW, Kim S, Yun MR, Kang HN, Pyo KH, Lee SS, Koh JS, Song HJ, Kim DK, Lee YS, Oh SW, Choi S, Kim HR, Cho BC. YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2019 Apr 15;25(8):2575-2587. doi: 10.1158/1078-0432.CCR-18-2906. Epub 2019 Jan 22.

  PMID: 30670498 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Brain Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Yuhan Corporation

  Clinical Development Department

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: February 8, 2017
• Study Start: February 15, 2017
• Primary Completion: January 8, 2021
• Study Completion: March 30, 2023
• Last Updated: March 21, 2025

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

KR (16)