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

Non-small Cell Lung Cancer Stage III Clinical Trial

— PLATINUM  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05338619
• Other study ID #: Korea-Lazertinib-CCRT
• Secondary ID: LASER IIT-010
• Status: Recruiting
• Phase: Phase 2
• Start date: June 30, 2022
• Est. completion date: March 2, 2026

Study information

• Verified date: August 2023
• Source: Korea University Guro Hospital
• Contact: Sung Yong Lee
• Phone: 82 2 2626 1914
• Email: syl0801[@]korea.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 77
• Est. completion date: March 2, 2026
• Est. primary completion date: March 2, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• EGFR Positive Non-small Cell Lung Cancer
• Lung Neoplasms
• Non-small Cell Lung Cancer Stage III
• Non-squamous Non-small-cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
Korea, Republic of	Kosin University Gospel Hospital	Busan
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital Hwasun Hospital	Gwangju
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Pusan National University Yangsan Hospital	Pusan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Hanyang University Seoul Hospital	Seoul
Korea, Republic of	Koera University Guro Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Kyung Hee University Hospital	Seoul
Korea, Republic of	Yonsei University Health System, Severance Hospital	Seoul

Sponsors (2)

Lead Sponsor	Collaborator
Sung Yong Lee	Yuhan Corporation

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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	Overall survival (OS)	The time from the date of enrollment until the date of death	Until death (up to maximum of approximately 4 years)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)