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Submitted by: Geraldine Guerina 2020-07-30 06:43:30 Last Updated by: Geraldine Guerina 2021-04-12 10:46:37


A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

PHRR200803-002780

YH25448-301

2020-CT0534

A Phase III, Randomized, Double-blind Study to Assess the Efficacy and Safety of Lazertinib versus Gefitinib as the First-line Treatment in Patients with Epidermal Growth Factor Receptor Sensitizing Mutation Positive, Locally Advanced or Metastatic Non-Small Cell Lung Cancer

This study is a randomized, double-blind, multinational phase III to assess the efficacy and safety of lazertinib 240 mg administered once daily orally compared with gefitinib 250 mg administered once daily orally in treatment-naïve patients with EGFR mutation positive (Ex19del or L858R substitution), locally advanced or metastatic NSCLC.

Start Date Duration in Months Target Completion Date Actual Completion Date
2020-08-31 46 2024-07-01 0000-00-00

Ongoing

Institution Classification Region LTO #
Yuhan Corporation Private Business South Korea
Institution Classification Region LTO #
PAREXEL Clinical Research (Philippines) Ltd. Corp. Private Business NCR LTO-3000006258189
Institution Region
Yuhan Corporation South Korea
Name E-Mail Institution and Institution Address
Cheryl L. Dy cheryl.dy@parexel.com Parexel Clinical Research (Philippines) Ltd. Corp., 15F Philam Life Tower, 8767 Paseo de Roxas, Makati City 1226 Philippines
Name E-Mail Institution and Institution Address
Akira Kojima, MD Akira.Kojima@parexel.com Parexel International, 13F Kayabacho Tower, 1-21-2, Shinkawa, Chuo-ku, Tokyo 104-0033, Japan
Name Expertise Affiliation
Adonis Guancia, MD Oncology Dr. Pablo O. Torre Memorial Hospital
Ellie May Villegas, MD Oncology Perpetual Succour Hospital
Guia Elena Imelda R. Ladrera, MD Oncology Lung Center of the Philippines
Jennifer Sandoval-Tan, MD Oncology Philippine General Hospital
Marie Cherry Lynn Samson-Fernando, MD Oncology Manila Doctors Hospital
Project Location Institutional Ethics Review Board
Dr. Pablo O. Torre Memorial Hospital Dr. Pablo O. Torre Memorial Hospital Research Ethics Review Committee
Perpetual Succour Hospital Perpetual Succour Hospital Institutional Ethics and Review Board
Lung Center of the Philippines Lung Center of the Philippines Ethics Review Committee
Philippine General Hospital Philippine General Hospital Ethics Review Board
Manila Doctors Hospital Manila Doctors Hospital Institutional Review Board

Non-small cell lung cancer (NSCLC)

To assess the efficacy of lazertinib compared with gefitinib as measued by progression-free survival (PFS)

To further assess the efficacy of lazertinib compared with gefitinib
To assess overall survival of lazertinib compared with gefitinib
To characterize the pharmacokinetics (PK) of lazertinib and its metabolite (YH26334)
To assess the impact of lazertinib compared with gefitinib on patient's disease-related symptoms and Health Related Quality of Life (HRQoL)

Completed

  • Australia
  • China
  • Greece
  • Hungary
  • Malaysia
  • Philippines
  • Russia
  • Serbia
  • Singapore
  • South Korea
  • Taiwan
  • Thailand
  • Turkey
  • Ukraine

Clinical Trial

YH25448-301

20200327100807

2020-07-13

0000-00-00

20

Unspecified

Unspecified

31 Aug 2020

Key Inclusion Criteria

Age and Sex
1. Male or female patients must be ≥ 18 years of age and satisfy the legal age of consent in the jurisdiction in which the study is being conducted.
Type of Patient and Disease Characteristics
2. Patients with pathologically confirmed adenocarcinoma of the lung (e.g., 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). Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
3. Patients with locally advanced or metastatic NSCLC, not amenable to curative surgery or radiotherapy.
4. Patients with at least 1 of the 2 common EGFR mutations known to be associated with EGFR TKI sensitivity (Ex19del or L858R), either alone or in combination with other EGFR mutations, assessed in tissue biopsy by an accredited local laboratory based on the Qiagen- Therascreen® EGFR Mutation Detection Kit RGQ (Scorpions ARMS), the Amoy Diagnostics-the AmoyDx® EGFR Mutation Test Kit, the PANAGENE-PANAMutyperTM or the Roche Diagnostics-Cobas® EGFR Mutation Test v2, or by central testing in a designated laboratory.
5. Mandatory provision of an unstained, archived tumor tissue sample in a quantity sufficient to allow for central analysis of EGFR mutation status for patients.
6. Patients must be treatment-naïve for locally advanced or metastatic NSCLC. (Note: Prior adjuvant and neo-adjuvant therapy (e.g., chemotherapy, radiotherapy, investigational products) for early stage disease is permitted if completed > 12 months prior to randomization provided all other entry criteria are satisfied)
7. Patients must have a WHO performance status score of 0 to 1 with no clinically significant deterioration over the previous 2 weeks before randomization.
8. Patients must have at least 1 measurable lesion, not previously irradiated and not chosen for biopsy during the study Screening period, that can be accurately measured at baseline as 210 mm in the longest diameter (except lymph nodes which must have a short axis of 215 mm) with computerized tomography (CT) or magnetic resonance imaging (MRI), and which is suitable for accurate repeated measurements. If only 1 measurable lesion exists, it is acceptable to be used (as a target lesion) as long as it has not been previously irradiated and baseline tumor assessment scans are done at least 2 weeks after the screening biopsy is performed.
Male Patients
9. A male patient who has not undergone a vasectomy must agree to follow the contraceptive guidance in Appendix 3 of this protocol during the study treatment period and for at least 24 weeks after the last dose of study treatment and refrain from donating sperm during this period.
Female Patients
10. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
· Not a woman of childbearing potential (WOCBP) as defined in Appendix 3. OR
· A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 from the time of screening until 24 weeks after the last dose of study treatment.
· A WOCBP must have a negative serum pregnancy test (beta human chorionic gonadotropin) at screening.
Informed Consent
11. Patient must sign an informed consent form (ICF) prior to any study specific procedures which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Key Exclusion Criteria

Medical Conditions
1. Symptomatic and unstable brain metastases. Patients with asymptomatic and stable brain metastases may participate in this study. If treatment is required, these patients must have completed any planned radiation therapy and/or surgery, are not on steroids, for >4 weeks prior to randomization, and remain asymptomatic. Patients must be neurologically stable, having no new neurologic deficits on clinical examination, and no new findings on central nervous system (CNS) imaging.
2. Leptomeningeal metastases
3. Symptomatic spinal cord compression. If steroid treatment is not required within at least 2 weeks prior to randomization then the patient may be enrolled.
4. History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
5. Any medical conditions requiring chronic continuous oxygen therapy.
6. History of any malignancy other than the disease under study within 3 years before randomization (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the medical monitor, is considered cured, or with minimal risk of recurrence within a year from screening).
7. Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the Investigator’s opinion makes it undesirable for the patient to participate in the study, or which would jeopardize compliance with the protocol.
8. Any cardiovascular disease as follows:
· History of symptomatic chronic heart failure or serious cardiac arrhythmia requiring active treatment.
· History of myocardial infarction or unstable angina within 24 weeks of randomization.
9. Positive hepatitis B (HBV) surface antigen (HBsAg), Positive hepatitis C antibody (anti-HCV), other clinically active infectious liver disease or confirmed positive human immunodeficiency virus test results. (Note: Patients with a prior history of HCV, who have completed antiviral treatment and have subsequently documented HCV RNA below the lower limit of quantification per local testing are eligible.)
10. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of study treatment.
11. History of hypersensitivity to active or inactive excipients of investigational product(s), or drugs with a similar chemical structure or class to investigational product(s).
12. Any history of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
13. Clinically significant chronic infection or significant medical or psychiatric illness.
14. Undergone a bone marrow or solid organ transplant.
15. Any condition which would prevent patient compliance with study procedures, restrictions, and requirements, as determined by the Investigator.
Prior/Concomitant Therapy
16. Prior treatment with any systemic antineoplastic therapy for locally advanced or metastatic NSCLC (Stage IIIB/C or Stage IV) including chemotherapy, biological therapy, immunotherapy, or any investigational drug.
17. Any prior treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI).
18. Major surgery (excluding placement of vascular access) within 4 weeks of randomization.
19. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of randomization.
20. Patients currently receiving (or unable to stop use for an appropriate washout period prior to randomization) medications or herbal supplements known to be potent CYP3A4 inhibitors or inducers (Appendix 6).
21. Patients who have been treated with alternative anti-cancer treatment within 5 half-lives of the treatment or within 4 weeks (whichever is longer) prior to randomization.
22. Any unresolved toxicities from prior therapy, greater than CTCAE grade 1 at randomization, with the exception of alopecia and grade 2, prior chemotherapy-induced neuropathy.
Prior/Concurrent Clinical Study Experience
23. Patients who have been treated with an investigational drug within 5 half-lives of the compound or within 4 weeks (whichever is longer) prior to randomization.
Diagnostic Assessments
24. Patient has any of following cardiac criteria:
· Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250msec).
· Mean resting QTc >470 msec obtained from 3 electrocardiograms (ECGs), using the screening ECG machine derived QTc value.
· Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age in first degree relatives or any concomitant medications known to prolong QT interval or induce Torsades de Pointes (Appendix 6).
· Left ventricular ejection fraction <50%
25. Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
· Absolute neutrophil count · Platelet count · Hemoglobin · Alanine aminotransferase >2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases, or >5x ULN in presence of liver metastases.

Interventional

Lazertinib

Lazertinib (YH25448) is an oral, highly potent, irreversible 3rd generation mutant selective and wild type sparing EGFR TKI that targets sensitizing EGFR mutations as well as the T790M mutation.

Date Amendment Classification Reason
2020-07-17 Amendments related to the protocol Informed consent
2020-09-07 Amendments related to the protocol Informed consent
2020-10-28 Amendments related to the protocol [1] Protocol YH25448-301 version 2 dated 03 Sep 2020; [2] IMPD (a) Lazertinib version dated 08 Sep 2020, (b) Placebo version dated 08 Sep 2020, (c) Over-encapsulated Gefitinib and Over-encapsulated Placebo version dated 08 Sep 2020
2021-03-10 Amendments related to the protocol IMPD (Lazertinib and Placebo) dated 22 Jan 2021, COVID-19 Memo (Patient Letter and Site Letter) version dated 28 Dec 2020

Randomized

Double Blind

Unspecified

Not Applicable

To assess the efficacy of lazertinib compared with gefitinib as measued by progression-free survival (PFS)

Phase III

Utilization Utilization Info
Publication
Oral Presentation
Drug Literature
Posters
Others
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