Clinical Trials /

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

NCT03046992

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Clinical Trial of YH25448 in Patients With EGFR Mutation Positive Advanced NSCLC
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: YH25448-201
  • NCT ID: NCT03046992

Conditions

  • EGFR Gene Mutation

Interventions

DrugSynonymsArms
YH25448YH25448

Purpose

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.

Detailed Description

      This is a first time in patient study primarily designed to evaluate the safety,
      tolerability, and efficacy of YH25448 in in patients with EGFR mutation positive (EGFRm+)
      advanced NSCLC with or without asymptomatic brain metastasis who progressed following prior
      therapy with an EGFR TKIs agent. This study is composed of 3 parts; part A is a dose
      escalation phase, part B is a dose expansion phase and part C is a dose extension phase.

      In dose escalation phase, YH25448 will be escalated to reach either a maximum tolerated or
      absorbable dose in patients as defined by dose-limiting toxicity in NSCLC patients who
      progressed following prior EGFR TKIs treatment to evaluate the safety and tolerability. In
      dose expansion phase, further safety, tolerability, pharmacokinetic(PK) and efficacy will be
      evaluated at each dose level(s) of dose escalation phase in NSCLC patients who progressed
      following prior EGFR TKIs treatment and harbouring confirmed T790M mutation. In dose
      extension phase, additional 3 cohorts (2nd line therapy cohort, 1st line therapy cohort, and
      brain metastasis cohort) will be enrolled to further assess the efficacy, safety,
      tolerability, and PK of YH25448 at the maximum tolerated dose (MTD) or recommended dose (RD)
      defined through dose escalation phase and dose expansion phase. Results of these studies will
      serve as the evidence for further clinical development.

      This study will also characterize the metabolite(s) profile of YH25448 and determine PK of
      its metabolite(s) in biological samples if necessary. Also, exploratory correlation between
      biomarker profiles and pharmacokinetics/pharmacodynamics will be analyzed.
    

Trial Arms

NameTypeDescriptionInterventions
YH25448ExperimentalDose Escalation Phase: Consists of 5 Cohorts Dose Expansion Phase: Consists of 4 Cohorts Dose Extension Phase: Consists of 3 Cohorts
  • YH25448

Eligibility Criteria

        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%
      
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability by Common Terminology Criteria for Adverse Events (CTCAE) v4.03
Time Frame:Safety and tolerability profile will be collected from baseline until 28 days after the last dose, expected average 1 year.
Safety Issue:
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.

Secondary Outcome Measures

Measure:Duration of Response (DoR)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT.
Measure:Disease Control Rate (DCR)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT.
Measure:Progression-Free Survival (PFS)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT. Kaplan-Meier plots will be used to summarize the progression-free survival.
Measure:Overall Survival (OS)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.
Measure:Tumor shrinkage
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.
Measure:Objective Intracranial Response Rate (OIRR)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.
Measure:Duration of Intracranial Response (DoIR)
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.
Measure:Intracranial Progression Free Survival (IPFS).
Time Frame:At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year.
Safety Issue:
Description:To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1. Kaplan-Meier plots will be used to summarize the progression-free survival.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Yuhan Corporation

Trial Keywords

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

Last Updated

July 1, 2017