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 : Unknown
Verified August 2021 by Yuhan Corporation.
Recruitment status was: Active, not recruiting
First Posted : February 8, 2017
Last Update Posted : August 11, 2021
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
EGFR Gene Mutation | Drug: YH25448 | Phase 1 Phase 2 |
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.
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 : | September 2022 |
Estimated Study Completion Date : | December 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: YH25448
|
Drug: YH25448
|
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
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.
Ages Eligible for Study: | 20 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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%
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
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 |
Study Director: | Yuhan Corporation | Clinical Development Department |
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: | August 11, 2021 |
Last Verified: | August 2021 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
EGFR Non-Small Cell Lung Cancer T790M Brain Metastasis |