A study to test the efficacy and safety of Lazertinib in the treatment of patients with Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 1

Conditions: Adenocarcinoma of the lung (non-small cell Lung cancer)
locally advanced or metastatic, not amenable to curative surgery or radiotherapy
MedDRA version: 21.0Level: LLTClassification code 10001165Term: Adenocarcinoma lung stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.0Level: LLTClassification code 10001164Term: Adenocarcinoma lung stage IIISystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 21.1Level: PTClassification code 10059515Term: Non-small cell lung cancer metastaticSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2019-004814-32-HU

Lead Sponsor: Yuhan Corporation

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 380

Inclusion Criteria

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
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 PANAGENEPANAMutyperTM 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 =10 mm in the longest diameter (except lymph nodes which must have a short axis of =15 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
9. A male patient who has not undergone a vasectomy must agree to follow the contraceptive guidance in Appendix 3 of 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
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 of protocol.
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.
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 protocol

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 380
F.1.3

Exclusion Criteria

1. Symptomatic and unstable brain metastases.
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
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.
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.
16. Prior treatment with any systemic antineoplastic therapy for locally advanced or metastatic NSCLC (IIIB/C or IV) including chemotherapy, biological therapy, immunotherapy, or any investigational drug.
17. Any prior treatment with an epidermal growth factor receptor-tyrosine kinase inhibitor.
18. Major surgery 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 medications or herbal supplements known to be potent CYP3A4 inhibitors or inducers
21. Patients receiving unstable doses of warfarin as anticoagulant
22. 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.
23. 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.
24. 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.
25. 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

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of lazertinib compared with gefitinib as measured by progression-free survival ;Secondary Objective: 1) To further assess the efficacy of lazertinib compared with gefitinib<br>2) To assess overall survival of lazertinib compared with gefitinib<br>3) To characterize the pharmacokinetics of lazertinib<br>4) To assess the impact of lazertinib compared with gefitinib on patient’s disease-related symptoms and Health Related Quality of Life <br>5) To assess the safety and tolerability profile of lazertinib compared with gefitinib;Primary end point(s): Progression-free survival according to RECIST v1.1 by Investigator assessment.<br><br>;Timepoint(s) of evaluation of this end point: October 2022

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): • Objective Response Rate (ORR)<br>• Duration of Response (DoR)<br>• Disease Control Rate (DCR)<br>• Depth of Response<br>• Time to Response<br>All according to RECIST v1.1 by Investigator assessments.<br>• Overall survival (OS)<br>• Plasma concentrations of lazertinib at pre-dose, 1 to 3 hours, and 4 to 6 hours post-dose<br>• Cerebrospinal fluid (CSF) concentrations of lazertinib<br>Change from baseline in :<br>• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 items (EORTC QLQ-C30)<br>• European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Lung Cancer 13 items (EORTC QLQ-LC13)<br>• Euro-Quality of Life-5 Dimension-5 (EQ-5D-5L) level (EQ-5D-5L)EQ-dd<br>;Timepoint(s) of evaluation of this end point: October 2022 and October 2024

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