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

Non-small Cell Lung Cancer Clinical Trial

— NeoLazer  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06268210
• Other study ID #: 4-2023-1546
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: March 2024
• Est. completion date: June 2028

Study information

• Verified date: February 2024
• Source: Yonsei University
• Contact: Hye Ryun Kim
• Phone: 82-2-2228-8125
• Email: nobelg[@]yuhs.ac
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 160
• Est. completion date: June 2028
• Est. primary completion date: June 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Severance hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	Pathologic Complete Response	Absence of detectable residual tumors in pathological findings after neoadjuvant therapy.	After neo adjuvant treatment(3months)
Secondary	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)
Secondary	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)
Secondary	Disease-Free Survival	Duration encompassing disease progression, recurrence, or death unrelated to the cause following surgical treatment.	End of trial(3years)
Secondary	Overall Survival	Duration from randomization to death unrelated to the cause.	End of trial(3years)
Secondary	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)