EU Commission Approves RYBREVANT® with Chemotherapy for Advanced EGFR-Mutated NSCLC After Prior Therapy Failure

In a significant development for lung cancer treatment, Janssen-Cilag International NV, a subsidiary of Johnson & Johnson, has secured approval from the European Commission for an expanded use of RYBREVANT® (amivantamab). This approval specifically allows the combination of amivantamab with chemotherapy agents carboplatin and pemetrexed to treat adults with advanced non-small cell lung cancer (NSCLC) characterized by specific EGFR mutations (Exon 19 deletions or Exon 21 L858R substitutions) following progression on an EGFR tyrosine kinase inhibitor (TKI).

The approval is particularly noteworthy as it addresses the pressing need for new treatment options for patients who have exhausted other EGFR-targeted therapies. These patients typically face poor prognoses and limited alternatives after disease progression. The amivantamab and chemotherapy combination has demonstrated a significant improvement in progression-free survival compared to chemotherapy alone, offering a new lifeline for these patients.

Dr. Antonio Passaro from the European Institute of Oncology in Milan highlighted the importance of this development. He emphasized that despite advancements in lung cancer treatment, resistance to existing therapies remains a considerable challenge. The addition of amivantamab to chemotherapy not only improves the overall response rate but also significantly reduces the risk of disease progression or death.

The approval is based on results from the Phase 3 MARIPOSA-2 study, which evaluated 657 patients with advanced or metastatic EGFR-mutant NSCLC. These patients had previously experienced disease progression on osimertinib, a commonly used EGFR TKI. The study revealed that the combination of amivantamab and chemotherapy reduced the risk of disease progression or death by 52%, achieving a median progression-free survival of 6.3 months compared to 4.2 months with chemotherapy alone. Additionally, the objective response rate with the combination treatment was 64% versus 36% for chemotherapy alone.

An important aspect of the study was its evaluation of intracranial progression-free survival, crucial for a disease where nearly 30% of patients develop brain metastases. Amivantamab combined with chemotherapy reduced the risk of intracranial progression or death by 45%, with a median intracranial progression-free survival of 12.5 months compared to 8.3 months for chemotherapy alone.

While the combination treatment has shown promising results, it is not without adverse effects. The safety profile was consistent with the known effects of each component, with Grade 3 or higher adverse events reported by 72% of patients on the combination therapy, compared to 48% on chemotherapy alone. Common adverse events included neutropenia, thrombocytopenia, anemia, and leukopenia. Serious adverse events were observed in 32% of patients receiving the combination treatment, compared to 20% on chemotherapy.

Dr. Henar Hevia, Senior Director at Johnson & Johnson, stated that this approval underscores the importance of precision medicine in enhancing outcomes for lung cancer patients. The MARIPOSA-2 study's findings were presented at the European Society for Medical Oncology (ESMO) 2023 Congress and published in the Annals of Oncology.

Amivantamab is a fully-human bispecific antibody targeting both EGFR and MET mutations. It represents a significant advancement in treating EGFR-mutant NSCLC, especially for those who have developed resistance to prior therapies. The approval of amivantamab in combination with chemotherapy provides a new and effective treatment strategy for a patient population with limited options, marking a step forward in the ongoing battle against lung cancer.