A Study of Lazertinib as Consolidation Therapy in Patients With Locally Advanced, Unresectable, EGFR-Mutant Non-Small Cell Lung Cancer (Stage III) Following Chemoradiation Therapy

Study Overview
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Brief Summary
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The PACIFIC trial confirmed that the consolidation therapy with durvalumab in patients with stage III, locally advanced, unresectable NSCLC that had not progressed after definitive platinum-based chemoradiation therapy improved the progression-free survival (PFS) by about 17 months. However, in PACIFIC, no significant differences between durvalumab and placebo were observed in PFS. Unmet need remains in development of successful consolidation therapy following chemoradiation therapy in patients with EGFR-mutant stage III unresectable NSCLC. A recent ADAURA study showed that Osimertinib as an adjuvant therapy after surgery significantly prolonged disease-free survival in EGFR mutation-positive patients. Lazertinib, like Osimertinib, is a third-generation EGFR TKI agent and has shown excellent anticancer effects in preclinical studies and in early clinical settings. Based on these results of the 3rd generation EGFR TKI, Lazertinib, it is expected that there is a clinical benefit Lazertinib as consolidation therapy. This study aims to investigate the clinical benefits of Lazertinib (Trade name: LECLAZA Tab) consolidation therapy for patients with EGFR mutation-positive, unresectable stage III NSCLC after definitive platinum-based chemoradiation therapy.

Detailed Description
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This study is designed as a prospective, open-label, single-arm, multicenter, phase II, investigator-initiated trial. A total of 77 patients will participate in the study who have undergone definitive platinum-based concurrent chemoradiation therapy and have no disease progression. Patients are to be enrolled within 1 to 42 days after concurrent chemoradiation therapy and to be administrated with lazertinib 240mg oral once daily until disease progression, or unacceptable toxicity. Patients will visit every 8 weeks and perform CT/MRI tumor evaluation by investigator, and will be followed up for survival every 3 months by phone thereafter. Patients will be followed up till maximum of appropriately 4 years of which 3 years since the last patient enrollment must be.

Official Title
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A Phase II, Multicenter Study of Lazertinib as Consolidation Therapy in Patients With Locally Advanced, Unresectable, EGFR Mutation Positive Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Chemoradiation Therapy (PLATINUM Trial)

Conditions
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EGFR Positive Non-small Cell Lung Cancer, Non-squamous Non-small-cell Lung Cancer, Non-small Cell Lung Cancer Stage III

Intervention / Treatment
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* Drug: Lazertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years and older Histologically and cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC) non-squamous cell carcinoma who present with locally advanced, unresectable, Stage III disease ECOG PS 0,1 Expected life expectancy of 6 months and more Patients who have received at least 2 cycles of definitive platinum-based concurrent chemoradiation therapy (CCRT) and who must be within 1 to 42 days after completion of radiation therapy Patients must not have had disease progression during or following CCRT Patients with adequate organ and bone marrow function Patients who give in written consent voluntarily to participate in this study Exclusion Criteria: History of interstitial lung disease, drug-induced interstitial lung disease, or radiation interstitial pneumonia History of other primary malignancy Mixed small cell and NSCLC histology Prior treatment with EGFR-TKI Therapy Unresolved toxicity of CTCAE grade 2 or higher following chemoradiation Current history of CTCAE grade 2 or higher pneumonia prior to chemoradiation therapy Patients with severe hypersensitivity to active ingredient or excipient of the investigational medicinal product Pregnant or breastfeeding patients Patients who do not agree to contraception with medically acceptable method for at least 6 months after the end of study intervention treatment Patients who participated in clinical trials within 4 weeks before participating in this study Judgment by the investigator that the patient is unsuitable to participate in this study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Lazertinib treatment group (open-label)
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lazertinib<br>Lazertinib 240mg, oral, QD | Drug: Lazertinib<br>* Lazertinib 240mg (3 Tabs as Laclaza Tab 80mg) once daily in oral can continue until disease progression, unacceptable toxicity or other discontinuation criteria are met.<br>* Other names: LECLAZA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival (PFS) | The time from the date of enrollment until the date of disease progression or death (by any cause in the absence of progression) Per RECIST 1.1 as assessed by Investigator. | Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | The time from the date of enrollment until the date of death | Until death (up to maximum of approximately 4 years) | 
| Objective response rate (ORR) | The number (%) of patient at least 1 visit response of Complete response (CR) or Partial response (PR). Per RECIST 1.1 as assessed by Investigator. | Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years) | 
| Duration of response (DoR) Duration of response (DoR) | The time from the date of first documented response until the first date of documented progression (or death in the absence of disease progression) Per RECIST 1.1 as assessed by Investigator. | Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years) | 
| Time to death or distant metastasis (TTDM) | The time from the date of enrollment until the first date of distant metastasis or death in the absence of distant metastasis. Per RECIST 1.1 as assessed by Investigator. | Until death or distant metastasis (up to maximum of approximately 4 years) | 
| Safety profile : Adverse Events according to CTCAE V5.0 | Adverse events, Serious adverse events or other significant safety findings | every visit (up to maximum of approximately 4 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NSCLC, Non-squamous cell carcinoma, EGFR, EGFR-TKI, Lazertinib