Lazertinib in Patients With NSCLC With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of EGFR TKI.
Primary Purpose
Lung Neoplasms
Status
Recruiting
Phase
Phase 2
Locations
Korea, Republic of
Study Type
Interventional
Intervention
lazertinib(YH25448)
Sponsored by
About this trial
This is an interventional treatment trial for Lung Neoplasms focused on measuring NSCLC, Brain Metastases, Failure of EGFR TKI
Eligibility Criteria
Inclusion Criteria
- Patients who voluntarily provided written informed consent prior to participation in the clinical trial and genetics and/or exploratory studies
- Male or female, 20 years of age or older(Female patients must agree to the use of appropriate contraceptive methods and not be lactating, and for women of childbearing age, there must be evidence that the pregnancy test is negative prior to initiation of dosing)
- Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer patients. This may occur as systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/C or IV disease.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, with no deterioration in the last 2 weeks
- Life expectancy judged by the Investigator of at least 3 months
- Asymptomatic or mild symptomatic brain metastases progressed or newly confirmed patients
- For one or more intracranial measurable disease, the maximum baseline diameter is measured to be 10mm or more on CT or MRI, and this lesions can be ccurately measured. (The target lesion that has received previous local therapy should not be considered as measurable. However, new CNS lesion after more than 3 months of previous local therapy could be considered as target lesion. )
- Confirmed sensitizing EGFR mutation prior to administration of gefitinib, erlotinib, or afatinib (L858R, Exon 19 deletion, G719X and L861Q mutations chould be confirmed as a record)
- Failure after one regimen of EGFR TKI treatment. Past treatment history for locally advanced or metastatic NSCLC limited to one regimen of EGFR TKI treatment (gefitinib, erlotinib, or afatinib) and/or one palliative cytotoxic chemotherapy regimen.
- Those who have been confirmed status of T790M mutations in tissues or blood after EGFR TKI failure (T790M positive or negative should be confirmed as a record)
Exclusion Criteria
- Prior treatment with lazertinib
- Prior treatment with investigational drugs in other clinical trials within 30 days prior to the first administration
- Patients who received cytotoxic chemotherapy for the treatment of advanced non-small cell lung cancer or other anticancer drugs other than EGFR TKI within 14 days prior to the first administration of the investigational drug
- Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment (e.g., major surgery, radiation therapy [with the exception of palliative bone-directed radiotherapy and radiotherapy administered to superficial lesions], hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)
- Patients currently receiving drugs or herbal supplements known as inhibitors or inducers of CYP3A4 or who cannot discontinue use at least 1 week prior to the first dose of lazertinib.
- Previous anticancer treatment-related toxicities not recovered to baseline or Grade 0-1 (except alopecia)
- Symptomatic spinal cord compression (However, registration is allowed if steroid treatment is not required within at least 2 weeks before the start of administration of the investigational drug)
- Symptomatic and unstable central nervous system (CNS) or brain metastasis requiring local treatment at screening. (Asymptomatic or mild symptomatic leptomeningeal metastasis is also permitted to be registered)
- Symptomatic or intracranial bleeding that needs treatment
- History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
- Carcinoma other than non-small cell lung cancer, if the investigator is judged to be inadequate to participate in this clinical trial due to evidence of severe or uncontrolled systemic disease, uncontrolled hypertension, or active bleeding tendency, or that it is difficult to follow this protocol. (Screening for chronic disease is not required)
- Any of the following cardiovascular diaseases: A history of congestive heart failure (CHF) of grade 3 or higher according to the New York Heart Association Classification (NYHA) or cardiac arrhythmia requiring treatment/A History of unstable angina or myocardial infarction experienced within 6 months before the first administration of the investigational drug/Left ventricular ejection fraction <50% on recent echocardiography or MUGA scan
- Known human immunodeficiency virus (HIV) infection
- Patient has known active hepatitis B virus(HBV) or hepatitis C virus (HCV) infection
- Patients with refractory nausea and vomiting, chronic gastrointestinal disorders, inability to swallow the product, or undergoing enterectomy deemed to interfere with the proper absorption of lazertinib.
- History of hypersensitivity to drugs
- Clinically significant chronic infection or major medical or mental illness
- Subjects with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the Investigators
- History of allogeneic hematopoietic stem cell transplantation, history of whole blood transfusions that did not remove leukocytes within 120 days before the date of collection of genetics specimens
Sites / Locations
- Seoul National University Bundang HospitalRecruiting
- Gachon University Gil Medical CenterRecruiting
- Korea University Anam HospitalRecruiting
- Seoul National University HospitalRecruiting
- Seoul St. Mary's Hospital, Catholic University of KoreaRecruiting
- Yonsei University Health System, Severance HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
lazertinib(YH25448)
Arm Description
lazertinib 240mg, once a day, oral, before disease progression
Outcomes
Primary Outcome Measures
Intracranial objective response rates (iORR) (RECIST1.1)
iORR will be evaluated according to RECIST v1.1 after IP administration and Response data will be used for the primary endpoint.
Secondary Outcome Measures
intracranial progression free survival, iPFS
the date of onset of objective intracranial disease progression or death of any cause, whichever occurs first.
iORR in T790M negative, isolated CNS progression patient group
iORR will be evaluated according to RECIST v1.1 after IP administration
overall ORR
ORR will be evaluated according to RECIST v1.1 after IP administration.
duration of response, DoR
Duration from the date of the first documented confirmatory response(CR or PR) to the date of documented disease progression or death (equivalent to the date of the PFS event)
disease control rate, DCR
the percentage of subjects whose response is CR, PR, responding, or SD.
overall survival, OS
the period from the first administration of the investigational drug to the date of death from any cause.
treatment failure pattern
intracranial progression or extracranial progression or both
salvage intracranial treatment rate
the percentag of subjects who received salvage treatment(surgery or radiation therapy) due to intracranial disease progression.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05326425
Brief Title
Lazertinib in Patients With NSCLC With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of EGFR TKI.
Official Title
Lazertinib in Patients With Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Metastatic Non-Small Cell Lung Cancer With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of EGFR Tyrosine Kinase Inhibitor
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 23, 2021 (Actual)
Primary Completion Date
June 30, 2024 (Anticipated)
Study Completion Date
June 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Jin Hyoung Kang
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
This is an open-label, single-intervention, multicenter clinical trial in patients with non-small cell lung cancer with asymptomatic or mildly symptomatic brain metastases after failure of EGFR TKI treatment. The objective of this study is as follows.
Primary objective : intracranial objective response rate (iORR) with RECIST 1.1
Secondary objectives : intracranial progression free survival(iPFS), Intracranial objective response rate in T790M negative, isolated CNS progression patient group, overall Objective Rsponse Rate(ORR), duration of response(DoR), disease control rate(DCR), treatment failure pattern): intracranial progression or extracranial progression or both, salvage intracranial treatment rate, safety and tolerability
Detailed Description
Patients who eligible the inclusion/exclusion criteria should take lazertinib 240 mg (80 mg, 3 tablets) once a day at the same time as possible on an empty stomach before meals. One cycle of treatment is defined as 42 days of continuous administration, and the tumor response by RECIST 1.1 will be evaluated every 1 cycle for the 1st, 2nd, 3rd, and 4th evaluation, and every 2 cycles from the 5th evaluation thereafter. .
If the investigator decides to reduce the dose due to an adverse drug reaction during the administration of lazertinib 240 mg, the dose may be reduced to 160 mg (80 mg, 2 tablets) of lazertinib.
Efficacy and safety will be evaluated by administering lazertinib 240 mg to patients with measurable brain metastasis or newly confirmed metastatic non-small cell lung cancer after failure of treatment with gefitinib, erlotinib, or afatinib after EGFR mutation is confirmed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lung Neoplasms
Keywords
NSCLC, Brain Metastases, Failure of EGFR TKI
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
lazertinib(YH25448)
Arm Type
Experimental
Arm Description
lazertinib 240mg, once a day, oral, before disease progression
Intervention Type
Drug
Intervention Name(s)
lazertinib(YH25448)
Intervention Description
- lazertinib 240mg(3tablets, 80mg/1tablet), once a day, oral, before disease progression
Primary Outcome Measure Information:
Title
Intracranial objective response rates (iORR) (RECIST1.1)
Description
iORR will be evaluated according to RECIST v1.1 after IP administration and Response data will be used for the primary endpoint.
Time Frame
From date of the first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary Outcome Measure Information:
Title
intracranial progression free survival, iPFS
Description
the date of onset of objective intracranial disease progression or death of any cause, whichever occurs first.
Time Frame
Up to 2 years
Title
iORR in T790M negative, isolated CNS progression patient group
Description
iORR will be evaluated according to RECIST v1.1 after IP administration
Time Frame
From date of the first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Title
overall ORR
Description
ORR will be evaluated according to RECIST v1.1 after IP administration.
Time Frame
From date of the first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Title
duration of response, DoR
Description
Duration from the date of the first documented confirmatory response(CR or PR) to the date of documented disease progression or death (equivalent to the date of the PFS event)
Time Frame
Up to 2 years
Title
disease control rate, DCR
Description
the percentage of subjects whose response is CR, PR, responding, or SD.
Time Frame
Up to 2 years
Title
overall survival, OS
Description
the period from the first administration of the investigational drug to the date of death from any cause.
Time Frame
Up to 2 years
Title
treatment failure pattern
Description
intracranial progression or extracranial progression or both
Time Frame
From date of the first administration until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Title
salvage intracranial treatment rate
Description
the percentag of subjects who received salvage treatment(surgery or radiation therapy) due to intracranial disease progression.
Time Frame
Up to 2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Patients who voluntarily provided written informed consent prior to participation in the clinical trial and genetics and/or exploratory studies
Male or female, 20 years of age or older(Female patients must agree to the use of appropriate contraceptive methods and not be lactating, and for women of childbearing age, there must be evidence that the pregnancy test is negative prior to initiation of dosing)
Histologically or cytologically confirmed locally advanced or metastatic non-small cell lung cancer patients. This may occur as systemic recurrence after prior surgery for early stage disease or patients may be newly diagnosed with stage IIIB/C or IV disease.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2, with no deterioration in the last 2 weeks
Life expectancy judged by the Investigator of at least 3 months
Asymptomatic or mild symptomatic brain metastases progressed or newly confirmed patients
For one or more intracranial measurable disease, the maximum baseline diameter is measured to be 10mm or more on CT or MRI, and this lesions can be ccurately measured. (The target lesion that has received previous local therapy should not be considered as measurable. However, new CNS lesion after more than 3 months of previous local therapy could be considered as target lesion. )
Confirmed sensitizing EGFR mutation prior to administration of gefitinib, erlotinib, or afatinib (L858R, Exon 19 deletion, G719X and L861Q mutations chould be confirmed as a record)
Failure after one regimen of EGFR TKI treatment. Past treatment history for locally advanced or metastatic NSCLC limited to one regimen of EGFR TKI treatment (gefitinib, erlotinib, or afatinib) and/or one palliative cytotoxic chemotherapy regimen.
Those who have been confirmed status of T790M mutations in tissues or blood after EGFR TKI failure (T790M positive or negative should be confirmed as a record)
Exclusion Criteria
Prior treatment with lazertinib
Prior treatment with investigational drugs in other clinical trials within 30 days prior to the first administration
Patients who received cytotoxic chemotherapy for the treatment of advanced non-small cell lung cancer or other anticancer drugs other than EGFR TKI within 14 days prior to the first administration of the investigational drug
Prior local-regional therapy within 4 weeks prior to Day 1 of trial treatment (e.g., major surgery, radiation therapy [with the exception of palliative bone-directed radiotherapy and radiotherapy administered to superficial lesions], hepatic arterial embolization, transcatheter arterial chemoembolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation)
Patients currently receiving drugs or herbal supplements known as inhibitors or inducers of CYP3A4 or who cannot discontinue use at least 1 week prior to the first dose of lazertinib.
Previous anticancer treatment-related toxicities not recovered to baseline or Grade 0-1 (except alopecia)
Symptomatic spinal cord compression (However, registration is allowed if steroid treatment is not required within at least 2 weeks before the start of administration of the investigational drug)
Symptomatic and unstable central nervous system (CNS) or brain metastasis requiring local treatment at screening. (Asymptomatic or mild symptomatic leptomeningeal metastasis is also permitted to be registered)
Symptomatic or intracranial bleeding that needs treatment
History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD
Carcinoma other than non-small cell lung cancer, if the investigator is judged to be inadequate to participate in this clinical trial due to evidence of severe or uncontrolled systemic disease, uncontrolled hypertension, or active bleeding tendency, or that it is difficult to follow this protocol. (Screening for chronic disease is not required)
Any of the following cardiovascular diaseases: A history of congestive heart failure (CHF) of grade 3 or higher according to the New York Heart Association Classification (NYHA) or cardiac arrhythmia requiring treatment/A History of unstable angina or myocardial infarction experienced within 6 months before the first administration of the investigational drug/Left ventricular ejection fraction <50% on recent echocardiography or MUGA scan
Known human immunodeficiency virus (HIV) infection
Patient has known active hepatitis B virus(HBV) or hepatitis C virus (HCV) infection
Patients with refractory nausea and vomiting, chronic gastrointestinal disorders, inability to swallow the product, or undergoing enterectomy deemed to interfere with the proper absorption of lazertinib.
History of hypersensitivity to drugs
Clinically significant chronic infection or major medical or mental illness
Subjects with any concurrent medical condition or disease that will potentially compromise the conduct of the study at the discretion of the Investigators
History of allogeneic hematopoietic stem cell transplantation, history of whole blood transfusions that did not remove leukocytes within 120 days before the date of collection of genetics specimens
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jin Hyoung Kang
Phone
82-2-2258-6043
Email
oncologykang@naver.com
First Name & Middle Initial & Last Name or Official Title & Degree
SuHyun Jeong
Phone
82-10-4679-7349
Email
tngusgmldud@naver.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jin Hyoung Kang
Organizational Affiliation
Seoul St. Mary's Hospital, The Catholic University of Korea
Official's Role
Study Chair
Facility Information:
Facility Name
Seoul National University Bundang Hospital
City
Gyeonggi-do
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yu Jung Kim
Phone
82-10-5265-9503
Email
cong1005@gmail.com
First Name & Middle Initial & Last Name & Degree
Yu Jung Kim
Facility Name
Gachon University Gil Medical Center
City
Incheon
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hee Kyung Ahn
Phone
82-10-9933-5099
Email
hkahn.onco@gmail.com
Facility Name
Korea University Anam Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ju Won Kim
Phone
82-10-6254-5546
Email
kohyot35@gmail.com
First Name & Middle Initial & Last Name & Degree
YoonJi Choi
Phone
82-10-8964-6724
Email
yj_choi@korea.ac.kr
First Name & Middle Initial & Last Name & Degree
Ju Won Kim
First Name & Middle Initial & Last Name & Degree
YoonJi Choi
Facility Name
Seoul National University Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bhumsuk Keam
Phone
82-10-3231-2208
Email
bhumsuk@snu.ac.kr
First Name & Middle Initial & Last Name & Degree
Bhumsuk Keam
Facility Name
Seoul St. Mary's Hospital, Catholic University of Korea
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
JIN HYOUNG KANG
Phone
82-2-2258-6043
Email
oncologykang@naver.com
First Name & Middle Initial & Last Name & Degree
SoHee Park
Phone
82-2-2258-6546
Email
vicky3018@naver.com
First Name & Middle Initial & Last Name & Degree
JIN HYOUNG KANG
Facility Name
Yonsei University Health System, Severance Hospital
City
Seoul
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hye Ryun Kim
Phone
82-10-8713-4793
Email
nobelg@yuhs.ac
First Name & Middle Initial & Last Name & Degree
Hye Ryun Kim
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
29293889
Citation
Goss G, Tsai CM, Shepherd FA, Ahn MJ, Bazhenova L, Crino L, de Marinis F, Felip E, Morabito A, Hodge R, Cantarini M, Johnson M, Mitsudomi T, Janne PA, Yang JC. CNS response to osimertinib in patients with T790M-positive advanced NSCLC: pooled data from two phase II trials. Ann Oncol. 2018 Mar 1;29(3):687-693. doi: 10.1093/annonc/mdx820.
Results Reference
result
PubMed Identifier
30670498
Citation
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.
Results Reference
result
PubMed Identifier
31587882
Citation
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. Erratum In: Lancet Oncol. 2020 Feb;21(2):e70.
Results Reference
result
Learn more about this trial
Lazertinib in Patients With NSCLC With Asymptomatic or Mild Symptomatic Brain Metastases After Failure of EGFR TKI.
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