A Randomized Study to Evaluate the Efficacy of a Reduced Starting Dose of Lazertinib (Leclaza) and Preemtive Magnesium Supplementation to Prevent Lazertinib(Leclaza)-Induced Peripheral Neuropathy

Phase 2RecruitingNCT07774520

Samsung Medical Center1,173 enrolled

Overview

Lazertinib is currently approved as a first-line treatment for EGFR-mutant NSCLC in South Korea. However, many patients experience peripheral neuropathy, which causes severe numbness, tingling, or painful muscle cramps. This side effect significantly lowers patients' quality of life and often leads to treatment interruptions. This phase 2, open-label, randomized clinical trial newly diagnosed EGFR mutant NSCLC patients is based on the hypothesis that a lower dose of lazertinib combined with magnesium supplementation will result in a more tolerable safety profile without compromising efficacy outcomes

Although lazertinib has been successfully established as a standard first-line targeted therapy for EGFR-mutant non-small cell lung cancer (NSCLC) in South Korea, its long-term clinical utility is frequently challenged by treatment limiting toxicities. Chief among these is peripheral neuropathy, which manifests as severe numbness, tingling sensations, or painful muscle cramps in the hands and feet. This distressing side effect not only profoundly impairs patients' daily functioning and overall quality of life but also frequently necessitates unplanned dose reductions or treatment interruptions, potentially compromising long-term oncological outcomes. To address this clinical unmet need, this phase 2, open-label, randomized clinical trial will evaluate 177 newly diagnosed patients to investigate optimization strategies aimed at mitigating nerve toxicity. The study is designed around the hypothesis that initiating treatment with a lower starting dose of lazertinib (160 mg/day) and introducing preemptive magnesium supplementation will significantly reduce the incidence of moderate-to-severe (Grade 2 or higher) peripheral neuropathy. Ultimately, the researchers aim to demonstrate that this novel intervention strategy can establish a highly tolerable safety profile, thereby preventing treatment interruptions and enhancing patient compliance, all while successfully maintaining the robust therapeutic efficacy of the core cancer treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

Eligibility

Sex: ALLMin age: 19 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Pathologically diagnosed pulmonary adenocarcinoma. 2. Patient with a stage not amenable to curative treatment by surgery or radiotherapy and requiring palliative chemotherapy. 3. Patient with no prior treatment history for lung cancer, or who relapsed \>=6 months after curative-intent therapy (concurrent chemoradiotherapy or adjuvant chemotherapy) with no subsequent anticancer treatment - i.e., a candidate for first-line chemotherapy. 4. Patient with a confirmed EGFR mutation of Exon 19 deletion or L858R. 5. Patient able to decide on participation in this study through voluntary decision-making. 6. Age 19 years or more. 7. ECOG PS 0-2. 8. Minimum life expectancy 12 weeks or more. 9. Adequate organ function. Exclusion Criteria: * Subjects with confirmed leptomeningeal/CNS metastasis on brain MRI or cerebrospinal fluid examination. * Subjects with pre-existing peripheral neuropathy. * Subjects who are taking any agent that may affect the development of peripheral neuropathy for reasons other than peripheral neuropathy (magnesium, pregabalin, gabapentin, duloxetine) and refuse to discontinue its use. * Subjects for whom, in the physician's judgment, participation in this study would carry greater harm than benefit (no specific items specified). * Uncontrolled systemic disease, including uncontrolled hypertension, severe heart failure, active bleeding, or active infection. * Pregnant or breastfeeding women. * History of interstitial lung disease (ILD), drug-induced ILD, radiation pneumonitis requiring steroid treatment, or evidence of clinically active ILD. * QTc prolongation based on QTc measured by ECG during the screening period (QTc \>=470 msec). * Subjects with a history of hypersensitivity to Magnes tablet. * Subjects with hereditary disorders of sugar metabolism such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption. * Subjects with a history of severe symptomatic renal failure. * Subjects taking a drug expected to have a clinically significant interaction when co-administered with magnesium-containing preparations - such as phosphate preparations, calcium preparations, oral tetracyclines, antacids, or levodopa - for whom discontinuation or substitution of the drug is not possible.

Outcomes

Primary Outcomes

Difference of grade 2 or higher peripheral neuropathy

To compare the incidence of grade 2 or higher peripheral neuropathy between the standard treatment arm (Arm 1: lazertinib 240 mg/day without magnesium supplementation) and the experimental arm (Arm 3: reduced-dose lazertinib 160 mg/day with magnesium supplementation).