Clinical trial · Interventional
Clinical Trial of YH25448 in Patients with EGFR Mutation Positive Advanced NSCLC
A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients with EGFR Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)
NCT03046992CI-TRIAL-00087555completedPhase 1 / Phase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| EGFR Gene Mutation | — | UNRESOLVED | — |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| YH25448 | Drug | Lazertinib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- YH25448
- description
- * Dose Escalation Phase: Consists of 7 Cohorts * Dose Expansion Phase: Consists of 5 Cohorts * Dose Extension Phase: Consists of 2 Cohorts
- interventionNames
- Drug: YH25448
Primary outcomes (2)
- measure
- Safety and tolerability by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
- timeFrame
- Safety and tolerability profile will be collected from baseline until 28 days after the last dose, expected average 1 year.
- description
- 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.
- measure
- Objective Response Rate (ORR)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 20 Years
Show eligibility criteria text
Inclusion Criteria: * 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. Exclusion Criteria: * 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%
References
Publications (5)
- DERIVEDHan 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
- DERIVEDKim 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
- DERIVEDCho 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
- DERIVEDAhn 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
- DERIVEDYun 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