Amivantamab-lazertinib is a combined drug regimen that serves as a targeted treatment for lung cancer. This therapy involves two distinct agents: amivantamab, a bispecific antibody, and lazertinib, a type of tyrosine kinase inhibitor (TKI). This combination is designed for patients diagnosed with non-small cell lung cancer (NSCLC) who possess particular genetic alterations within their tumors. This regimen advances precision oncology, offering a focused approach to combat cancer cells with these characteristics.
Dual-Target Mechanism of Action
Cancer cell growth is often driven by abnormal signals, particularly those involving the Epidermal Growth Factor Receptor (EGFR) protein. EGFR is a protein found on the surface of cells, and when it is mutated in certain ways, it can send continuous growth signals, leading to uncontrolled cell division and tumor formation. Lazertinib works by acting inside the cancer cell, specifically targeting and blocking these abnormal signals emanating from the mutated EGFR. This action stops the internal machinery of the cancer cell from growing and dividing, thereby inhibiting tumor progression.
Amivantamab operates on the exterior of the cancer cell. It is a bispecific antibody, meaning it can bind to two different targets simultaneously. Amivantamab binds to the EGFR protein on the cell surface, which prevents growth signals from reaching the cell’s interior and also marks the cancer cell for destruction by the body’s immune system.
Amivantamab also targets another protein called MET, implicated in cancer cells developing resistance to EGFR-blocking therapies. By engaging both EGFR and MET, amivantamab addresses pathways through which cancer cells might evade treatment. The combined use of lazertinib and amivantamab creates a synergistic effect, attacking the cancer cell from both internal signaling pathways and external cell surface interactions, while also counteracting common resistance mechanisms.
Indications for Use
The treatment targets a subset of non-small cell lung cancer (NSCLC) characterized by specific genetic changes in the epidermal growth factor receptor (EGFR) gene. These include EGFR exon 19 deletions or the L858R substitution in exon 21. These are common activating mutations that make the cancer responsive to this targeted therapy.
The amivantamab-lazertinib combination is approved as a first-line treatment option, meaning it is for patients who have not received prior systemic therapy for their locally advanced or metastatic disease. Before initiating this therapy, patients must undergo genetic testing of their tumor tissue. This testing confirms the presence of these specific EGFR mutations, ensuring the treatment is appropriate and effective for their cancer.
Clinical Efficacy and Outcomes
The efficacy of amivantamab-lazertinib has been evaluated in clinical trials, such as the Phase 3 MARIPOSA study. This international, randomized trial compared the combination therapy against osimertinib, a standard single-agent treatment, in previously untreated patients with advanced EGFR-mutated NSCLC. The study assessed the combination’s performance in delaying disease progression and improving patient outcomes.
Progression-Free Survival (PFS) indicates the length of time a patient lives with the disease without it worsening. In the MARIPOSA trial, patients receiving amivantamab-lazertinib demonstrated a median PFS of 23.7 months, longer than 16.6 months for those treated with osimertinib. This represents a statistically significant improvement in delaying disease progression.
The Overall Response Rate (ORR) is the percentage of patients whose tumors shrink. The MARIPOSA study reported an ORR of 86% for the combination therapy, similar to the 85% observed with osimertinib. The Duration of Response (DoR) measures how long the treatment keeps the cancer in check for responders. The median DoR for the amivantamab-lazertinib group was 25.8 months, longer than the 16.8 months seen with osimertinib alone. Initial analyses also indicated a favorable trend in overall survival.
Management of Adverse Events
The amivantamab-lazertinib combination can cause side effects. These reactions are managed by the oncology team. Common side effects associated with this regimen include skin and nail issues, such as rash (observed in up to 86% of patients) and paronychia (infected skin around the nail, seen in up to 71%).
Patients may also experience infusion-related reactions (IRRs) due to amivantamab, particularly during the first infusion. Other frequent adverse events include diarrhea (up to 31%), swelling (edema) (up to 36%), and sores in the mouth (stomatitis, up to 43%). These common side effects are managed with supportive medications, dose adjustments, or proactive strategies like premedication for infusion reactions and topical treatments.
More serious, though less common, side effects can occur, requiring prompt medical attention. These include interstitial lung disease (ILD) or pneumonitis, and venous thromboembolism (VTE) or blood clots. Proactive measures like prophylactic anticoagulation during the initial four months of treatment have been implemented to mitigate the risk of VTEs. Close monitoring by the healthcare team is part of managing these effects, ensuring patient safety and treatment continuity.
Treatment Administration and Patient Experience
The administration of amivantamab-lazertinib involves both intravenous and oral components. Amivantamab is given as an intravenous (IV) infusion, typically in a clinic or hospital setting. The initial treatment schedule for amivantamab usually involves weekly infusions for the first month, followed by a maintenance schedule of infusions every two weeks thereafter.
To manage infusion-related reactions, the very first infusion of amivantamab is often administered using a “split-dosing” approach, where the total dose is divided and given over two days. Lazertinib, conversely, is an oral medication taken as a pill at home, typically once a day. This oral component offers convenience for patients, allowing easier integration into daily routines.
Patients undergoing this combination therapy will experience a time commitment for their infusion days, which varies depending on infusion rate and necessary pre-medications or monitoring. Adherence to the daily oral lazertinib medication schedule is also important for the overall effectiveness of the treatment.