What Is Lazertinib?
Lazertinib is a drug being studied for various forms of lung cancer. It is a third-generation Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI). This type of medication works by targeting specific mutations in the EGFR, a protein that can promote cancer cell growth. By inhibiting the activity of mutated EGFR, lazertinib aims to slow or stop the growth of cancer cells.
Lazertinib is primarily being investigated for the treatment of non-small cell lung cancer (NSCLC), especially in patients with specific EGFR mutations like T790M. Clinical trials are exploring its use as a monotherapy and in combination with other anti-cancer drugs, such as amivantamab and chemotherapy regimens like pemetrexed and carboplatin. These studies aim to evaluate its effectiveness and safety in different treatment settings, including first-line therapy and in cases where resistance to other treatments has developed.
Uses and Conditions Under Study
Lazertinib is being studied for its potential to treat several conditions, primarily focusing on different types of lung cancer. The most common conditions under investigation include various forms of non-small cell lung cancer (NSCLC). These encompass Non-Small-Cell Lung Carcinoma (7 trials), Non-small Cell Lung Cancer (5 trials), Non Small Cell Lung Cancer (5 trials), and NSCLC (2 trials), totaling 19 trials across these similar descriptions.
Non-small cell lung cancer is a type of cancer that starts in the lungs and accounts for most lung cancer cases. Lazertinib, as an EGFR TKI, is designed to target specific genetic mutations often found in NSCLC cells, which can drive tumor growth. By blocking these signals, the drug aims to inhibit cancer progression.
Additionally, Lazertinib is being studied for specific genetic markers associated with lung cancer, such as EGFR T790M (2 trials), a mutation known to cause resistance to earlier generations of EGFR inhibitors. Broader categories like Lung Cancer (1 trial), Lung Cancer Stage IV (1 trial), and Lung Neoplasms (1 trial) are also being explored, indicating its potential use across different stages and manifestations of the disease.
Beyond cancer treatment, Lazertinib is also being evaluated in Healthy participants (6 trials). These studies typically focus on understanding how the drug is absorbed, distributed, metabolized, and excreted in the body, as well as its safety profile, rather than treating a specific disease.
Dosing
Lazertinib is primarily administered in oral forms. Clinical trials have investigated various dosing strategies, most commonly involving daily oral intake. The most frequently studied strength is 240 mg, taken once a day (QD). For instance, some trials specify "Lazertinib 240 mg PO QD" or "Lazertinib 240mg/day" as a continuous daily oral dose until disease progression or unacceptable toxicity.
Another strength, 160 mg, has also been explored in certain study arms. Lazertinib is often studied as a monotherapy, but it is also frequently combined with other treatments. In combination regimens, such as with amivantamab or with chemotherapy like pemetrexed and carboplatin, Lazertinib typically maintains its 240 mg once-daily oral administration.
The drug's administration is being evaluated in various study designs, including single arms, combination arms, and specific sequences of treatments. Different cohorts within trials explore how Lazertinib interacts with other drugs or how it performs in specific patient populations, such as those with hepatic impairment, where different dosing groups (e.g., Group 1: Moderate Hepatic Impairment; Group 2: Normal Hepatic Function) are assessed. There is no information provided regarding specific pediatric dosing; all described dosages pertain to adult participants.
Side Effects
In a clinical trial involving 421 patients treated with Lazertinib, the most common side effect was paronychia (inflammation around the fingernail or toenail). 68.4% of patients taking Lazertinib experienced paronychia, compared to 28.4% on placebo.
Other common side effects included:
- Infusion-related reactions occurred in 62.0% of patients on Lazertinib, while no patients on placebo experienced this.
- Rash was reported in 61.8% of patients taking Lazertinib, compared to 35.3% on placebo.
- Hypoalbuminaemia (low albumin levels in the blood) affected 48.5% of patients on Lazertinib, versus 6.7% on placebo.
- Increased alanine aminotransferase (a liver enzyme) was observed in 36.1% of patients taking Lazertinib, compared to 15.9% on placebo.
- Peripheral edema (swelling, typically in the legs or arms) occurred in 35.6% of patients on Lazertinib, compared to 7.5% on placebo.
- Constipation was reported in 29.0% of patients taking Lazertinib, compared to 14.2% on placebo.
- Dermatitis acneiform (an acne-like skin condition) affected 29.0% of patients on Lazertinib, versus 15.6% on placebo.
Diarrhea was also reported, but was less common in patients taking Lazertinib (29.2%) than in those on placebo (40.1%).
Clinical Trial Results
Clinical trials have evaluated the effectiveness of Lazertinib in patients with Epidermal Growth Factor Receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC), both as a standalone treatment and in combination with other therapies.
Lazertinib Monotherapy in Advanced NSCLC (NCT04075396)
In a study of Lazertinib as a monotherapy, different doses were investigated. The disease control rate (DCR), meaning the percentage of patients whose cancer either shrank or remained stable, was 60.0% for patients receiving 240 mg of Lazertinib and 53.8% for those receiving 320 mg. The objective response rate (ORR), indicating the percentage of patients whose cancer significantly shrank, was 26.7% for the 240 mg dose and 7.7% for the 320 mg dose. Patients on the 240 mg dose had a median overall survival (OS) of 9.1 months, while those on the 320 mg dose had a median OS of 7.7 months. The median progression-free survival (PFS) was 3.1 months for the 240 mg dose and 4.2 months for the 320 mg dose.
Lazertinib Versus Gefitnib as First-Line Treatment (NCT04248829)
A study comparing Lazertinib 240 mg to gefitnib 250 mg as a first-line treatment for EGFR mutation-positive NSCLC showed similar disease control and objective response rates. Both Lazertinib and gefitnib arms had a disease control rate of 93.9%. The objective response rate was 76.0% for Lazertinib and 76.1% for gefitnib. However, Lazertinib demonstrated a longer median progression-free survival (PFS) of 20.6 months, compared to 9.7 months for gefitnib. The median duration of response (DoR) was also longer with Lazertinib at 19.4 months, versus 8.3 months for gefitnib.
Lazertinib in Combination Therapies
Several trials have explored Lazertinib in combination with other drugs:
- In a study comparing combination therapy to osimertinib (NCT04487080), patients receiving Lazertinib plus a placebo matching osimertinib had a median progression-free survival (PFS) of 18.46 months. The combination of amivantamab and Lazertinib resulted in a median PFS of 23.72 months, while osimertinib plus a placebo matching Lazertinib had a median PFS of 16.59 months.
- For patients with EGFR-mutated NSCLC after osimertinib failure (NCT04988295), a combination of Lazertinib, amivantamab, carboplatin, and pemetrexed (LACP/ACP-L) showed a median progression-free survival (PFS) of 8.31 months. This was longer than carboplatin and pemetrexed alone (4.17 months) or amivantamab with carboplatin and pemetrexed (6.28 months).
- Another study (NCT05388669) investigated Lazertinib combined with amivantamab, comparing subcutaneous (SC) versus intravenous (IV) administration of amivantamab. This trial primarily focused on the drug levels of amivantamab, showing that the area under the concentration-time curve (AUC) for amivantamab was similar for both SC and IV routes when combined with Lazertinib.
Currently Recruiting Trials
Several clinical trials are currently recruiting participants to further investigate Lazertinib, often in combination with other therapies, primarily for non-small cell lung cancer (NSCLC). These studies aim to understand how well these treatments work and their safety profiles.
- One Phase 2 study, sponsored by Janssen Research & Development, LLC, is comparing amivantamab in combination with Lazertinib against amivantamab with platinum-based chemotherapy. This trial, NCT06667076, is for participants with common epidermal growth factor receptor (EGFR)-mutated locally advanced or metastatic NSCLC and plans to enroll up to 480 individuals.
- Another Phase 2 study, NCT06106802, from Samsung Medical Center, is evaluating Lazertinib alongside tepotinib. This trial focuses on EGFR mutant NSCLC in patients whose cancer has progressed after previous Lazertinib treatment and shows MET overexpression or amplification, targeting 47 participants.
- Janssen Research & Development, LLC is also sponsoring NCT06120140, a Phase 2 study exploring enhanced dermatological care. This trial aims to reduce rash and paronychia in EGFR-mutated NSCLC patients treated first-line with amivantamab plus Lazertinib, with an enrollment goal of 300 participants.
- The National Cancer Center, Korea, is conducting NCT06156527, a Phase 2 trial comparing Lazertinib alone versus Lazertinib plus bevacizumab for NSCLC with EGFR mutations in smokers. This study is designed for 120 participants.
- A Phase 2 study, NCT05541822, sponsored by Abion Inc, is assessing vabametkib as a monotherapy or in combination with Lazertinib. This trial is for patients with advanced solid tumors harboring c-MET dysregulation, with an enrollment target of 178.
- Janssen Research & Development, LLC is also recruiting for NCT05498428, a Phase 2 study of amivantamab in participants with advanced or metastatic solid tumors, including EGFR-mutated NSCLC. This study has a substantial enrollment target of 520 participants.
- Konkuk University Medical Center is running NCT05469022, a Phase 2 trial investigating neoadjuvant Lazertinib therapy in EGFR-mutation positive lung adenocarcinoma detected by BALF liquid biopsy, aiming for 40 participants.
- Finally, Yonsei University is sponsoring NCT06268210, a Phase 2 study of neoadjuvant Lazertinib with or without chemotherapy for patients with EGFR-mutated resectable non-small cell lung cancer. This trial plans to enroll 160 participants.
Where to Participate
Clinical trials for Lazertinib are broadly available across the United States, with study sites in 36 states, encompassing 135 cities and a total of 181 locations. This wide reach helps ensure accessibility for many potential participants.
The top cities with multiple recruiting sites include:
- Boston, Massachusetts (4 sites)
- Atlanta, Georgia (4 sites)
- Los Angeles, California (4 sites)
- San Francisco, California (4 sites)
- Glendale, California (4 sites)
- Walnut Creek, California (3 sites)
- Orange, California (3 sites)
- Fairfax, Virginia (3 sites)
- Orlando, Florida (3 sites)
- Washington D.C., District of Columbia (3 sites)
Eligibility for these studies generally includes adults aged 18 and older, regardless of gender. Healthy volunteers and children are not eligible to participate.
Development Timeline
The journey of Lazertinib in clinical development began on November 20, 2015, with the latest trial projected to conclude by April 2, 2026. Since its inception, a total of 40 clinical trials have been initiated, enrolling approximately 8,908 participants across various phases.
Early in its development, Lazertinib was explored for conditions such as IBS-C and hyperphosphatemia. However, the focus quickly shifted and significantly expanded to address various forms of lung cancer, particularly non-small cell lung cancer (NSCLC) with specific EGFR mutations. The pipeline now also includes investigations into advanced solid tumors and c-MET dysregulation.
The majority of studies have progressed into Phase 2, with 22 trials reaching this stage, indicating a strong commitment to evaluating efficacy and safety in larger patient populations. There have been 9 Phase 1 trials, 4 Phase 3 trials, and 1 Phase 1/Phase 2 study. Janssen Research & Development, LLC has been a primary driver of Lazertinib's development, sponsoring 16 trials, alongside significant contributions from institutions like Yonsei University, Yuhan Corporation, and Samsung Medical Center.