Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer (NeoLazer)

Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer (NeoLazer): a Phase II, Randomized, Multi-center Study

In the randomized, multicenter Phase II clinical trial, we aim to evaluate the efficacy and safety of Lazertinib monotherapy or the combination of Lazertinib and cytotoxic chemotherapy as neoadjuvant therapy in patients with resectable, treatment-naive EGFR-mutant (exon 19 deletion or exon 21 L858R) non-small cell lung cancer, ranging from clinical stage IB to IIIB. The study is designed to assess the impact on pathological response, as well as effectiveness and safety considerations.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Lazertinib+Pemetrexed+Carboplatin; Drug: Lazertinib

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hye Ryun Kim; Phone Number: 82-2-2228-8125; Email: nobelg@yuhs.ac

Study Locations

• South Korea
  • Seoul, South Korea
    • Recruiting
    • Severance Hospital
    • Contact: Hye Ryun Kim; Phone Number: 82-2-2228-8125; Email: nobelg@yuhs.ac

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. At the time of providing consent, the patient must be an adult aged 19 years or older.
2. Must have histologically or cytologically confirmed completely resectable, non-squamous non-small cell lung cancer (according to AJCC 8th edition, stages IB-IIIB).
3. Complete surgical resection must be deemed feasible based on the investigator's determination and in accordance with local treatment practices. This decision must be verified through the collaboration of a multidisciplinary team, including surgical oncologists, medical oncologists, and radiation oncologists. (Methods of surgical resection: either lobectomy or segmentectomy)
4. Documented presence of EGFR activating mutations (EGFR exon 19 deletion or L858R mutation).
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

6. Adequate and normal organ and bone marrow function, defined as follows:

   Hemoglobin: ≥9.0 g/dL Absolute neutrophil count: ≥1.5 × 10^9/L Platelet count: ≥100 × 10^9/L Serum bilirubin: ≤1.5 x upper limit of normal (ULN) ALT and AST: ≤2.5 x ULN Creatinine clearance: ≥50 ml/min or serum creatinine ≤1.5 × ULN

7. Life expectancy of more than 6 months.

8. Female patients must agree to use appropriate contraceptive methods, should not be breastfeeding, and if of childbearing potential, must have evidence of non-pregnancy through a negative pregnancy test prior to initiation. Effective contraception should be maintained for up to 3 months after the last dose of Lazertinib (6 months for Pemetrexed/Carboplatin).

   Women over 50 years who have discontinued all exogenous hormone therapy and have been amenorrheic for at least 12 months, considered in a "postmenopausal" state.

   Irreversible surgical infertility due to hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; tubal ligation is not allowed.

   Women under 50 years should be considered in a postmenopausal state if they have discontinued all exogenous hormone therapy for at least 12 months, with LH and FSH levels within the postmenopausal range per the testing institution's criteria.

9. Male patients who have not undergone vasectomy must agree to barrier contraception, specifically condom use, and effective contraception and sperm donation are prohibited for up to 3 months after the last dose of Lazertinib (6 months for Pemetrexed/Carboplatin).

Exclusion Criteria:

1. If there is evidence of locally advanced and/or metastatic disease (Stage IIIC-IV).
2. Known positive status for human immunodeficiency virus (HIV).
3. Evidence of severe or uncontrolled active infections, including chronic active hepatitis B and/or C; patients with chronic hepatitis B virus (HBV) with low viral load (HBV DNA ≤ 500 IU/mL or ≤ 2500 copies/mL) can participate if appropriate antiviral therapy can be continued during the treatment period.
4. Evidence of severe or uncontrolled systemic diseases such as uncontrollable hypertension, active bleeding, etc.
5. History of solid organ transplantation.
6. History of interstitial lung disease (ILD) requiring steroid treatment or clinically active ILD.
7. History of malignancies other than non-small cell lung cancer within the past 3 years at the time of the first dose of the investigational drug (exceptions: treated cervical intraepithelial neoplasia, differentiated thyroid cancer without lymph node involvement, non-melanoma skin cancer).
8. Intractable nausea and vomiting, gastrointestinal disorders, or patients for whom oral administration is not feasible, and those deemed to have absorption disorders that may interfere with Lazertinib absorption, with the exception of cases where clinically significant absorption disorders are not present, as determined by the investigator, in patients who have undergone colon resection.
9. Pregnant or lactating women.

10. Any of the following cardiac criteria:

    Average QT interval corrected for heart rate (QTcF) > 470 msec based on three electrocardiogram (ECG) measurements taken with the screening ECG equipment.

    Clinically significant abnormalities in rhythm, conduction, or morphology at rest on ECG, such as complete left bundle branch block, third-degree heart block, second-degree heart block, PR interval > 250 msec.

    Clinically significant heart failure, congenital long QT syndrome, known concomitant drug administration that prolongs the QT interval, or any factors that increase the risk of QTc prolongation or arrhythmias, such as a family history of QTc prolongation or sudden death under the age of 40.

11. Known hypersensitivity to the active or inactive ingredients of Lazertinib or drugs with a similar chemical structure or belonging to the same class.
12. If, in the investigator's judgment, a patient is unlikely to comply with the clinical trial procedures, restrictions, and requirements, and it is determined that the patient should not participate in the clinical trial.
13. Currently participating or planning to participate in any other interventional clinical trial excluding non-interventional clinical trials.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental; Patients will receive a combination therapy of Lazertinib and Pemed-S + Carboplatin as neoadjuvant treatment before surgery, followed by post-surgery maintenance with Lazertinib at a dosage of 240 mg once daily for a duration of 3 years. Dosages: Lazertinib: 240 mg once daily (pre-/post-surgery for 3 years) Pemetrexed: 500 mg/m2 every 3 weeks (neoadjuvant therapy for 3 cycles) Carboplatin: AUC5 every 3 weeks (neoadjuvant therapy for 3 cycles)	Drug: Lazertinib+Pemetrexed+Carboplatin; Lazertinib: 240 mg once daily (pre-/post-surgery for 3 years) Pemetrexed: 500 mg/m2 every 3 weeks (neoadjuvant therapy for 3 cycles) Carboplatin: AUC5 every 3 weeks (neoadjuvant therapy for 3 cycles)
Active Comparator: Comparator; Lazertinib will be administered at a dosage of 240 mg once daily, both before and after surgery, for a duration of 3 years.	Drug: Lazertinib; Lazertinib will be administered at a dosage of 240 mg once daily, both before and after surgery, for a duration of 3 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary pathological response	Primary pathological response refers to the condition where the proportion of viable tumor cells is defined as 10% or less, indicating a substantial reduction in the survival of tumor cells.	After neo adjuvant treatment(3months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surgical Resection Methods (Segmentectomy or Lobectomy)	Surgical techniques defined by thoracic surgeons based on the extent of surgical resection during radical surgery.	After radical surgery(3months)
Pathologic Complete Response	Absence of detectable residual tumors in pathological findings after neoadjuvant therapy.	After neo adjuvant treatment(3months)
Objective Response Rate	Percentage of patients exhibiting complete response (CR) or partial response (PR) based on RECIST 1.1 criteria from radiological examinations performed prior to surgical treatment.	After surgery(3months)
Event-Free Survival	Duration encompassing disease progression in situations where surgical treatment has not been carried out following randomization, excluding disease progression leading to surgical exclusion, disease progression or recurrence post-surgical treatment, or death unrelated to the cause.	End of trial(3years)
Disease-Free Survival	Duration encompassing disease progression, recurrence, or death unrelated to the cause following surgical treatment.	End of trial(3years)
Overall Survival	Duration from randomization to death unrelated to the cause.	End of trial(3years)
Number of patients with Adverse events according to CTCAE v5.0	Evaluation of the safety profile of the protocol treatment summarized in a table for all safety parameters, including: Adverse events according to CTCAE v5.0, including instances leading to treatment interruption, permanent discontinuation, or death.; Severe, serious, or specified adverse events.; Death.; Laboratory parameters, abnormal findings, and vital signs.	End of trial(3years)

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Hye Ryun Kim, Severance Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: February 8, 2024
• First Submitted That Met QC Criteria: February 12, 2024
• First Posted (Actual): February 20, 2024

Study Record Updates

• Last Update Posted (Actual): February 9, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Folic Acid Antagonists; lazertinib
• Other Study ID Numbers: 4-2023-1546

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