EGFR Mutant, Non-small Cell Lung Cancer(NSCLC)
Conditions
Brief summary
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
Detailed description
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.
Interventions
DRUGSupplementation of magnesium lactate
Supplementation of magnesium lactate
DRUGDose reduction of lezertinib
Dose reduction of lazertinib 240mg to 160mg qd
Sponsors
Samsung Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference of grade 2 or higher peripheral neuropathy | From date of randomization until the date of first documented progression or date of death from any cause, or onset of peripheral neuropathy assessed up to 36 months | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression free survival between different lazertinib starting dose | From date of randomization until the date of first documented progression or date of death from any cause, or onset of peripheral neuropathy assessed up to 36 months | The difference in progression free survival between the two different lazertinib starting-dose groups, Arm 1 and 2 which are treated with lazertinib 240mg, and Arm 3 with reduced dose of lazertinib 160mgTime |
| Overall survival between different lazertinib starting dose | From date of randomization until the date of first documented progression or date of death from any cause, or onset of peripheral neuropathy assessed up to 36 months | The difference in overall survival between the two different lazertinib starting-dose groups, Arm 1 and 2 which are treated with lazertinib 240mg, and Arm 3 with reduced dose of lazertinib 160mg |
| Improvement of lazertinib reduction or supplement of magnesium in peripheral neuropathy | From development of peripheral neuropathy up to 12 weeks | In Arm 1 (lazertinib 240 mg/day without magnesium supplement) or Arm 2 (lazertinib 240 mg/day with magnesium supplement), the rate at which peripheral neuropathy improves to grade 1 or grade 0 following lazertinib dose reduction (160 mg/day) and/or additional magnesium use, when grade 2 or higher peripheral neuropathy develops during the study |
| Difference in grade 2 or higher peripheral neuropathy between two experimental arm 2 and 3 | From date of randomization until the date of first documented progression or date of death from any cause, or onset of peripheral neuropathy assessed up to 36 months | The difference in the incidence of grade 2 or higher peripheral neuropathy between the two experimental arms (Arms 2 and 3, Arm 2 is patient with lazertinib 240mg with magnesium supplement, and Arm 3 is patient with lazertinib 160mg with magnesium supplement), To evaluate the effect of magnesium supplement in different lazertinib dose |
| Objective response rate between different lazertinib starting dose | From date of randomization until the date of first documented progression or date of death from any cause, or onset of peripheral neuropathy assessed up to 36 months | The difference in objective response rate between the two different lazertinib starting-dose groups, Arm 1 and 2 which are treated with lazertinib 240mg, and Arm 3 with reduced dose of lazertinib 160mg |
Countries
South Korea
Contacts
CONTACTJonmu Sun Sun, MD,PhD
Outcome results
None listed