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

NCT06268210 | Recruiting Phase 2

• 1 other identifier: 4-2023-1546
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Surgical Resection Methods (Segmentectomy or Lobectomy)

  After radical surgery(3months)

• Pathologic Complete Response

  After neo adjuvant treatment(3months)

• Objective Response Rate

  After surgery(3months)

• Event-Free Survival

  End of trial(3years)

• Disease-Free Survival

  End of trial(3years)

Study Arms (2)

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

Comparator

ACTIVE 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

Interventions

Lazertinib+Pemetrexed+Carboplatin DRUG

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)

Experimental

Lazertinib DRUG

Lazertinib will be administered at a dosage of 240 mg once daily, both before and after surgery, for a duration of 3 years.

Comparator

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At the time of providing consent, the patient must be an adult aged 19 years or older.
• Must have histologically or cytologically confirmed completely resectable, non-squamous non-small cell lung cancer (according to AJCC 8th edition, stages IB-IIIB).
• 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)
• Documented presence of EGFR activating mutations (EGFR exon 19 deletion or L858R mutation).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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
• Life expectancy of more than 6 months.
• 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.
• 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).

You may not qualify if:

• If there is evidence of locally advanced and/or metastatic disease (Stage IIIC-IV).
• Known positive status for human immunodeficiency virus (HIV).
• 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.
• Evidence of severe or uncontrolled systemic diseases such as uncontrollable hypertension, active bleeding, etc.
• History of solid organ transplantation.
• History of interstitial lung disease (ILD) requiring steroid treatment or clinically active ILD.
• 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).
• 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.
• Pregnant or lactating women.
• 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.
• Known hypersensitivity to the active or inactive ingredients of Lazertinib or drugs with a similar chemical structure or belonging to the same class.
• 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.

Sponsors & Collaborators

• Yonsei University: lead

Study Sites (1)

Severance hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

lazertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Hye Ryun Kim

  Severance Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hye Ryun Kim

CONTACT

82-2-2228-8125; nobelg@yuhs.ac

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 8, 2024
• First Posted: February 20, 2024
• Study Start: February 7, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)