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 (PLATINUM)

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer Stage III; Non-squamous Non-small-cell Lung Cancer; EGFR Positive Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Lazertinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 77
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sung Yong Lee; Phone Number: 82 2 2626 1914; Email: syl0801@korea.ac.kr
• Study Contact Backup: Name: Youngsun Cho; Phone Number: 82 70 4820 0249; Email: choyoungsun@procuratio.kr

Study Locations

• Korea, Republic of
  • Busan, Korea, Republic of
    • Recruiting
    • Kosin University Gospel Hospital
    • Contact: Jang; Phone Number: 82 51 990 6637
    • Principal Investigator: Tae Won Jang, MD, PhD
  • Daegu, Korea, Republic of
    • Recruiting
    • Keimyung University Dongsan Hospital
    • Contact: Park; Phone Number: 82 53 258 4519
    • Principal Investigator: Sun Hyo Park, MD, PhD
  • Daegu, Korea, Republic of
    • Recruiting
    • Kyungpook National University Medical Center
    • Contact: Shin Yup Lee, MD, PhD; Phone Number: 82 53 200 3091
  • Daejeon, Korea, Republic of
    • Recruiting
    • Chungnam National University Hospital
    • Contact: Lee; Phone Number: 82 42 280 6135
    • Principal Investigator: Jeong Eun Lee, MD, PhD
  • Gwangju, Korea, Republic of
    • Recruiting
    • Chonnam National University Hospital Hwasun Hospital
    • Contact: Oh; Phone Number: 82 61 379 7869
    • Principal Investigator: In-Jae Oh, MD, PhD
  • Incheon, Korea, Republic of
    • Recruiting
    • Inha University Hospital
    • Contact: Lim; Phone Number: 82 32 890 3894
    • Principal Investigator: Jun Hyeok Lim, MD, MS
  • Pusan, Korea, Republic of
    • Recruiting
    • Pusan National University Yangsan Hospital
    • Contact: Seong Hoon Yoon, MD, PhD; Phone Number: 82 55 360 1415
  • Seoul, Korea, Republic of
    • Recruiting
    • Asan Medical Center
    • Contact: Choi; Phone Number: 82 2 3010 8358
    • Principal Investigator: Chang-Min Choi, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Su In Choi, MD, PhD; Phone Number: 82 2 920 5439
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Kim; Phone Number: 82 2228 2268
    • Principal Investigator: Eunyoung Kim, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Hanyang University Seoul Hospital
    • Contact: Park; Phone Number: 82 2 2290 9065
    • Principal Investigator: Dong Won Park, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Koera University Guro Hospital
    • Contact: Lee; Phone Number: 82 2 2626 1914
    • Principal Investigator: Sung Yong Lee, MD, PhD
    • Sub-Investigator: Juwhan Choi, MD, PhD
  • Seoul, Korea, Republic of
    • Recruiting
    • Kyung Hee University Hospital
    • Contact: Lee; Phone Number: 82 2 958 8511
    • Principal Investigator: Seung Hyeun Lee, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 18 years and older
2. 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
3. ECOG PS 0,1
4. Expected life expectancy of 6 months and more
5. 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
6. Patients must not have had disease progression during or following CCRT
7. Patients with adequate organ and bone marrow function
8. Patients who give in written consent voluntarily to participate in this study

Exclusion Criteria:

1. History of interstitial lung disease, drug-induced interstitial lung disease, or radiation interstitial pneumonia
2. History of other primary malignancy
3. Mixed small cell and NSCLC histology
4. Prior treatment with EGFR-TKI Therapy
5. Unresolved toxicity of CTCAE grade 2 or higher following chemoradiation
6. Current history of CTCAE grade 2 or higher pneumonia prior to chemoradiation therapy
7. Patients with severe hypersensitivity to active ingredient or excipient of the investigational medicinal product
8. Pregnant or breastfeeding patients
9. Patients who do not agree to contraception with medically acceptable method for at least 6 months after the end of study intervention treatment
10. Patients who participated in clinical trials within 4 weeks before participating in this study
11. Judgment by the investigator that the patient is unsuitable to participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lazertinib; Lazertinib 240mg, oral, QD	Drug: Lazertinib; 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.; Other Names: LECLAZA

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes form baseline in different biomarkers	Biomarker evaluations include tumor-educated platelets (TFP), circulating tumor DNA(ctDNA), and peripheral blood mononuclear cells (PMBCs). It will be investigated to understand the better and long-term survival, drug-resistant mechanism and hematology in occurrence of pneumonitis.	Pre-dose(within 6 week of completion of CCRT), after 8-week dosing, and confirmed disease progression (approximately 15 months)

Collaborators and Investigators

• Sponsor: Sung Yong Lee
• Collaborators: Yuhan Corporation
• Investigators: Principal Investigator: Sung Yong Lee, MD, PhD, Korea University Guro Hospital

Publications and helpful links

General Publications

• Choi J, Lee JE, Choi CM, Oh IJ, Lee KY, Jang TW, Lee SH, Kim EY, Park DW, Park SH, Lee SY. 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). Thorac Cancer. 2022 Dec;13(23):3431-3435. doi: 10.1111/1759-7714.14663. Epub 2022 Oct 19.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2022
• Primary Completion (Estimated): March 2, 2026
• Study Completion (Estimated): March 2, 2026

Study Registration Dates

• First Submitted: April 14, 2022
• First Submitted That Met QC Criteria: April 14, 2022
• First Posted (Actual): April 21, 2022

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 31, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; EGFR; EGFR-TKI; Lazertinib; Non-squamous cell carcinoma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Lazertinib
• Other Study ID Numbers: Korea-Lazertinib-CCRT; LASER IIT-010 (Other Grant/Funding Number: YUHAN Coorporation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No