Clinical trial NCT05338619: 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
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer Stage III
EGFR Positive Non-small Cell Lung Cancer
Non-squamous Non-small-cell Lung Cancer
Keywords: NSCLC
Non-squamous cell carcinoma
EGFR
EGFR-TKI
Lazertinib
Lead sponsor: Korea University Guro Hospital
Sponsor class: OTHER
Collaborators: name: Yuhan Corporation
First posted: 2022-04-21
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Lazertinib treatment group (open-label)
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Progression free survival (PFS)
timeFrame: Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years)
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Until death (up to maximum of approximately 4 years)
measure: Objective response rate (ORR)
timeFrame: Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years)
measure: Duration of response (DoR) Duration of response (DoR)
timeFrame: Tumor scan will be performed at baseline the every 8 weeks until confirmed disease progression (up to 4 years)
measure: Time to death or distant metastasis (TTDM)
timeFrame: Until death or distant metastasis (up to maximum of approximately 4 years)
measure: Safety profile : Adverse Events according to CTCAE V5.0
timeFrame: every visit (up to maximum of approximately 4 years)
Other outcomes:
measure: Changes form baseline in different biomarkers
timeFrame: Pre-dose(within 6 week of completion of CCRT), after 8-week dosing, and confirmed disease progression (approximately 15 months)
Locations:
city: Busan
country: Korea, Republic of
facility: Kosin University Gospel Hospital
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital Hwasun Hospital
city: Incheon
country: Korea, Republic of
facility: Inha University Hospital
city: Pusan
country: Korea, Republic of
facility: Pusan National University Yangsan Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Hanyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Koera University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: Korea University Guro Hospital
name: Sung Yong Lee, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.