Lazertinib before surgery, alone or with chemotherapy, for EGFR-mutated resectable lung cancer

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

This trial tests whether giving lazertinib alone or with chemotherapy before surgery helps adults with resectable EGFR-mutated non-small cell lung cancer (stages IB–IIIB).

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 20 Years and up
• Sex: All
• Sponsor: Yonsei University (Academic / other)
• Drugs / interventions: Lazertinib, radiation, chemotherapy
• Locations: 1 site (Seoul)
• Trial ID: NCT06268210 on ClinicalTrials.gov

What this trial studies

This randomized multicenter Phase II trial assigns adults with treatment‑naive, resectable non‑squamous NSCLC harboring EGFR exon 19 deletion or exon 21 L858R to receive neoadjuvant lazertinib alone or lazertinib combined with pemetrexed and carboplatin. The planned treatment is given before surgery with the intent of improving pathological tumor response and enabling complete resection. Key eligibility includes clinical stage IB–IIIB disease, ECOG 0–1, and adequate organ function, with multidisciplinary confirmation of resectability. The study will monitor pathological response rates, surgical outcomes, and safety signals related to the targeted agent and chemotherapy combination.

Who should consider this trial

Good fit: Ideal candidates are adults (≥19) with treatment‑naive, resectable non‑squamous NSCLC carrying an EGFR exon 19 deletion or exon 21 L858R mutation, clinical stage IB–IIIB, ECOG 0–1, and adequate organ and marrow function.

Not a fit: Patients with squamous histology, non‑resectable or metastatic disease, other/unknown EGFR mutations, prior systemic therapy for this cancer, poor performance status, or inadequate organ function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, this approach could shrink tumors before surgery and increase rates of complete (pathologic) response and potentially improve long‑term outcomes.

How similar studies have performed: Prior neoadjuvant EGFR‑TKI trials (for example with osimertinib, gefitinib, or erlotinib) have shown promising pathological responses, but lazertinib and its combination with platinum‑pemetrexed remain less well studied in this setting.

Eligibility criteria

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.

Where this trial is running

Seoul

• Severance hospital — Seoul, South Korea (Recruiting)

Study contacts

• Principal investigator: Hye Ryun Kim — Severance Hospital
• Study coordinator: Hye Ryun Kim

Conditions Non-small Cell Lung Cancer