European Commission Approves Amivantamab for Advanced NSCLC Treatment
Patients with EGFR ex19del or EGFR L858R mutations, which are the most prevalent mutations in non-small cell lung cancer (NSCLC), have historically faced a grim prognosis and limited treatment options after their disease progresses on previous therapies.
Amivantamab, when combined with chemotherapy, is the first treatment regimen to demonstrate a significant improvement in progression-free survival compared to chemotherapy alone for this patient group.
Janssen-Cilag International NV, a subsidiary of Johnson & Johnson, announced that the European Commission (EC) has granted a Type II extension of indication for RYBREVANT (amivantamab) in conjunction with chemotherapy (carboplatin and pemetrexed). This treatment is specifically for adults with advanced NSCLC who have EGFR Exon 19 deletions (ex19del) or L858R substitutions and have experienced disease progression after prior therapy, including an EGFR tyrosine kinase inhibitor (TKI).
Dr. Antonio Passaro, a medical oncologist at the European Institute of Oncology, highlighted the advancements in lung cancer treatments in recent years. He pointed out that resistance to existing therapies remains a significant hurdle for patients with advanced NSCLC who have EGFR mutations, underscoring the urgent need for continued innovation in this field.
He added that introducing the bispecific antibody amivantamab alongside chemotherapy offers a crucial new treatment option for patients who have progressed on or after osimertinib. This combination has set a new benchmark for overall response rates and has significantly decreased the risk of disease progression or death by more than half when compared to standard chemotherapy. Additionally, it showed marked improvements in intracranial progression-free survival, which is vital given that NSCLC often spreads to the brain.
Dr. Henar Hevia, Senior Director and EMEA Therapeutic Area Lead in Oncology at Johnson & Johnson, stated that this approval meets a significant unmet need for patients whose disease has advanced following earlier treatment with an EGFR TKI and have few treatment options left.
The expanded indication for amivantamab is based on results from the Phase 3 MARIPOSA-2 study, which assessed the efficacy and safety of amivantamab combined with chemotherapy in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who experienced disease progression after osimertinib treatment. The study revealed that this combination therapy significantly lowered the risk of disease progression or death by 52 percent compared to chemotherapy alone, with a median progression-free survival of 6.3 months versus 4.2 months.
Moreover, the study reported an objective response rate of 64 percent for the amivantamab plus chemotherapy group, in contrast to 36 percent for those receiving chemotherapy alone. The data also indicated that this combination had intracranial activity, which is particularly relevant since nearly 30 percent of patients with advanced NSCLC develop brain metastases.
The combination of amivantamab and chemotherapy reduced the risk of intracranial progression or death by 45 percent, achieving a median intracranial progression-free survival of 12.5 months compared to 8.3 months for chemotherapy alone.
The safety profile of the amivantamab and chemotherapy combination was consistent with that of the individual components. Adverse events of Grade 3 or higher occurred in 72 percent of patients treated with the combination, while 48 percent of those receiving chemotherapy alone reported similar adverse events. The most common Grade 3 or higher adverse events included neutropenia, thrombocytopenia, anemia, and leukopenia.
Serious treatment-related adverse events leading to death were rare across all treatment groups, occurring in only 2 percent of patients receiving the combination therapy and in 1 percent of those receiving chemotherapy alone.
Dr. Kiran Patel, Vice President of Clinical Development for Solid Tumours at Johnson & Johnson, described the approval as a crucial advancement in transforming the treatment landscape for individuals living with lung cancer. He reaffirmed the company's dedication to enhancing a comprehensive lung cancer portfolio, particularly through precision medicine approaches that aim to redefine care standards.
Importance of the MARIPOSA-2 Study
The results of the MARIPOSA-2 study were presented during a Presidential Symposium at a recent congress and were simultaneously published in a prominent oncology journal. This randomized, open-label Phase 3 trial involved 657 patients and evaluated the efficacy and safety of two combination regimens of amivantamab (with and without another investigational therapy) alongside chemotherapy.
All participants underwent serial brain imaging to facilitate a thorough assessment of intracranial endpoints, further emphasizing the study’s focus on a critical area of high unmet need.
Overview of Amivantamab
Amivantamab is a fully-human bispecific antibody that targets both EGFR and MET alterations. It is designed to utilize the immune system to target tumors with these mutations, which are common in various cancers.
The European Commission has granted marketing authorization for amivantamab across multiple indications, including its use in combination therapies for treating adults with advanced NSCLC characterized by specific activating mutations. The drug has shown significant potential in improving treatment outcomes for this challenging patient population.
Future Directions
Several regulatory applications are currently in progress to further expand the indications for amivantamab. The company is actively exploring innovative solutions to adapt to the evolving landscape of cancer treatment.
Frequently Asked Questions
What is Amivantamab?
Amivantamab is a bispecific antibody that targets EGFR and MET mutations, providing a new treatment option for patients with advanced NSCLC.
How does Amivantamab work?
It targets tumors with specific mutations, utilizing the immune system to enhance the effectiveness of cancer treatments.
What is the significance of the MARIPOSA-2 study?
The study demonstrated that combining Amivantamab with chemotherapy significantly improves progression-free survival and overall response rates in patients with advanced NSCLC.
What are the common side effects of Amivantamab?
Common side effects include hematologic toxicities such as neutropenia, anemia, and thrombocytopenia, though serious adverse events are relatively low.
Is Amivantamab approved for other treatments?
Yes, it has received marketing authorization for various indications concerning patients with advanced NSCLC with specific mutations.
