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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03046992
Recruitment Status : Active, not recruiting
First Posted : February 8, 2017
Last Update Posted : March 20, 2020
Sponsor:
Information provided by (Responsible Party):
Yuhan Corporation

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.

Condition or disease Intervention/treatment Phase
EGFR Gene Mutation Drug: YH25448 Phase 1 Phase 2

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 2 cohorts (2nd line therapy cohort, 1st line therapy 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Actual Study Start Date : February 15, 2017
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: YH25448
  • Dose Escalation Phase: Consists of 7 Cohorts
  • Dose Expansion Phase: Consists of 5 Cohorts
  • Dose Extension Phase: Consists of 2 Cohorts
Drug: YH25448
  • Dose Escalation: YH25448 20mg~320mg, PO
  • Dose Expansion: YH25448 40mg~240mg, PO
  • Dose Extension: Recommended Dose 240mg of YH25448




Primary Outcome Measures :
  1. 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. ]
    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.

  2. Objective Response Rate (ORR) [ Time Frame: At baseline and every 6 weeks from first dose objective disease progression or withdrawal from study, up to approximately 1 year. ]
    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.


Secondary Outcome Measures :
  1. 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. ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT.

  2. 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. ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT.

  3. 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. ]
    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.

  4. 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. ]
    To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.

  5. 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. ]
    To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.

  6. 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. ]
    To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.

  7. 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. ]
    To obtain assessment of anti-tumor activity of YH25448 by evaluation of tumor response using RECIST version 1.1.

  8. 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. ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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%

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03046992


Locations
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Korea, Republic of
Chungbuk National University Hospital
Cheongju-si, Chungcheongbuk-do, Korea, Republic of, 28644
The Catholic University of Korea, Bucheon St. Mary's Hospital
Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647
National Cancer Center
Goyang-si, Gyeonggi-do, Korea, Republic of, 03080
CHA Bundang Medical Center, CHA University
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13496
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
The Catholic University of Korea, St. Vincent's Hospital
Suwon-si, Gyeonggi-do, Korea, Republic of, 16247
Gyeongsang National University Hospital
Jinju-si, Gyeongsangnam-do, Korea, Republic of, 52727
Inje University Haeundae Paik Hospital
Busan, Korea, Republic of, 48108
Gachon University Gil Medical Center
Incheon, Korea, Republic of, 21565
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Kangbuk Samsung Hospital
Seoul, Korea, Republic of, 03181
Asan Medical Center
Seoul, Korea, Republic of, 05505
Samsung Medical Center
Seoul, Korea, Republic of, 06351
SMG-SNU Boramae Medical Center
Seoul, Korea, Republic of, 07061
Severance Hospital
Seoul, Korea, Republic of
Ulsan University Hospital
Ulsan, Korea, Republic of, 44033
Sponsors and Collaborators
Yuhan Corporation
Investigators
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Study Director: Yuhan Corporation Clinical Development Department
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Yuhan Corporation
ClinicalTrials.gov Identifier: NCT03046992    
Other Study ID Numbers: YH25448-201
First Posted: February 8, 2017    Key Record Dates
Last Update Posted: March 20, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Yuhan Corporation:
EGFR
Non-Small Cell Lung Cancer
T790M
Brain Metastasis