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

NCT07774520 | Recruiting Phase 2

• 1 other identifier: SMC 2026-06-08
• Study Type: interventional
• Target: 1,173
• Locations: 1 country
• Sites: 1

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

Conditions

Non-small Cell Lung Cancer(NSCLC); EGFR Mutant

Outcome Measures

Primary Outcomes (1)

• 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).

  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

Secondary Outcomes (5)

• 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

• 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

• 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

• 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

• Improvement of lazertinib reduction or supplement of magnesium in peripheral neuropathy

  From development of peripheral neuropathy up to 12 weeks

Study Arms (3)

Arm 1

NO INTERVENTION

Lazertinib 240mg without magnesium supplement

Arm 2

ACTIVE COMPARATOR

Lazertinib 240mg with magnesium lactate supplement

Drug: Supplementation of magnesium lactate

Arm 3

EXPERIMENTAL

Reduced dose of Lazertinib(160mg) with magnesium supplement

Drug: Supplementation of magnesium lactate; Drug: Dose reduction of lezertinib

Interventions

Supplementation of magnesium lactate DRUG

Supplementation of magnesium lactate

Arm 2; Arm 3

Dose reduction of lezertinib DRUG

Dose reduction of lazertinib 240mg to 160mg qd

Arm 3

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologically diagnosed pulmonary adenocarcinoma.
• Patient with a stage not amenable to curative treatment by surgery or radiotherapy and requiring palliative chemotherapy.
• 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.
• Patient with a confirmed EGFR mutation of Exon 19 deletion or L858R.
• Patient able to decide on participation in this study through voluntary decision-making.
• Age 19 years or more.
• ECOG PS 0-2.
• Minimum life expectancy 12 weeks or more.
• Adequate organ function.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Samsung Medical Center: lead

Study Sites (1)

Samsung Medical Center

Seoul, Gang-nam Gu, 06351, South Korea

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Jonmu Sun Sun, MD,PhD

CONTACT

82-2-3410-3459; jongmu.sun@samsung.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 17, 2026
• First Posted: August 19, 2026
• Study Start: May 26, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)