Clinical trial NCT06268210: Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-small Cell Lung Cancer
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2024-02-20
Enrollment: 160
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Primary pathological response
timeFrame: After neo adjuvant treatment(3months)
Secondary outcomes:
measure: Surgical Resection Methods (Segmentectomy or Lobectomy)
timeFrame: After radical surgery(3months)
measure: Pathologic Complete Response
timeFrame: After neo adjuvant treatment(3months)
measure: Objective Response Rate
timeFrame: After surgery(3months)
measure: Event-Free Survival
timeFrame: End of trial(3years)
measure: Disease-Free Survival
timeFrame: End of trial(3years)
measure: Overall Survival
timeFrame: End of trial(3years)
measure: Number of patients with Adverse events according to CTCAE v5.0
timeFrame: End of trial(3years)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Severance hospital
Study officials:
affiliation: Severance Hospital
name: Hye Ryun Kim
role: PRINCIPAL_INVESTIGATOR
References: