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Arm A will receive Lazertinib and Pemetrexed, Carboplatin combination. Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity. Pemetrexed(500 mg/m2) will be administered IV infusion on Day 1 of each 21-day cycle until disease progression or unacceptable toxicity. Carboplatin(AUC5) will be administered IV infusions on Day 1 of each 21-day cycle until 4 cycles.

Lazertinib+Pemetrexed+Carboplatin

Lazertinib will be given 240 mg once a day daily PO until disease progression or unacceptable toxicity.

Sun Min Lim

Lazertinib is an oral third-generation irreversible tyrosine kinase inhibitor (TKI) that has proved to selectively inhibit EGFR-TKI sensitizing mutations (exon 19 deletion or exon 21 L858R) and be effective in patients with central nervous system (CNS) metastases. However, all patients eventually experience disease progression. For patients with MRD, lazertinib plus cytotoxic anticancer drug can prolong the duration of response or even induce complete cure, indicating this combined treatment strategy is considered the safest and most effective.

The objective of this phase 2 prospective two-arm clinical trial is to evaluate the safety and efficacy of lazertinib alone or in combination with cytotoxic chemotherapy in EGFR-mutant (exon 19 deletion or exon 21 L858R) NSCLC patients without ctDNA clearance after lead-in lazertinib. If anticancer drugs are used only for patients with MRD, the risk of resistance development will decrease, improving PFS.

Hypothesis: to evaluate the efficacy defined as the PFS rate of lazertinib alone or in combination with a cytotoxic anticancer drug in EGFR-mutant NSCLC patients without ctDNA clearance after lead-in lazertinib monotherapy.

Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy

A Randomized, Phase 2 Trial of Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy (CHAMELEON)

PFS is measured from the date of start of study to the date of disease progression or death from any cause.

Yonsei University

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)

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

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)

Hye Ryun Kim

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.

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

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.

Surgical techniques defined by thoracic surgeons based on the extent of surgical resection during radical surgery.

Absence of detectable residual tumors in pathological findings after neoadjuvant therapy.

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.

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.

Duration encompassing disease progression, recurrence, or death unrelated to the cause following surgical treatment.

Duration from randomization to death unrelated to the cause.

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy	NCT06020989	Non Small Cell ...	Lazertinib+Peme... Lazertinib Lazertinib	19 Years -	Yonsei University
Neoadjuvant Lazertinib With or Without Chemotherapy for Patients With EGFR-mutated Resectable Non-small Cell Lung Cancer	NCT06268210	Non-small Cell ...	Lazertinib+Peme... Lazertinib	20 Years -	Yonsei University
Lazertinib and Chemotherapy Combination in EGFR-mutant NSCLC Patients Without ctDNA Clearance After lead-in Lazertinib Monotherapy	NCT06020989	Non Small Cell ...	Lazertinib+Peme... Lazertinib Lazertinib	19 Years -	Yonsei University

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