Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the European Commission (EC) has approved a Type II extension of indication for RYBREVANT®▼ (amivantamab) in combination with chemotherapy (carboplatin and pemetrexed), for the treatment of adults with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 19 deletions (ex19del) or Exon 21 L858R substitution (L858R) mutations, after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI).
“While much progress has been made in the lung cancer treatment landscape over the past decade, resistance to existing therapies continues to pose a major challenge for patients with advanced or metastatic non-small cell lung cancer harbouring EGFR mutations, underscoring the critical need for ongoing innovation,” said Antonio Passaro, M.D., Ph.D., Medical Oncologist, Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy. “The addition of the bispecific antibody amivantamab to chemotherapy offers an important new treatment option for patients with EGFR ex19del or L858R mutations, progressing on or after osimertinib. In this setting, this combination set the new landmark for overall response rate and reduced the risk of disease progression or death by more than half compared to standard chemotherapy alone. It also demonstrated significant improvements in intracranial progression-free survival.”
“The approval of amivantamab in combination with chemotherapy addresses a major unmet need for those whose disease has progressed following treatment with an EGFR TKI and who, until now, have faced limited treatment options,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “This milestone further reinforces the critical role of precision medicine in driving enhanced outcomes for patients living with lung cancer.”
The expanded indication for amivantamab is based on results from the Phase 3 MARIPOSA-2 study (NCT04988295), evaluating the efficacy and safety profile of amivantamab and chemotherapy in patients with locally-advanced or metastatic EGFR ex19del or L858R substitution NSCLC who had disease progression on or after treatment with osimertinib. The amivantamab plus chemotherapy arm met its primary endpoint, significantly reducing the risk of disease progression or death by 52 percent, compared to chemotherapy alone, with a median progression-free survival (PFS) of 6.3 months, versus 4.2 months (hazard ratio [HR]=0.48; 95 percent confidence interval [CI], 0.36–0.64; P<0.001). Additionally, amivantamab plus chemotherapy showed an objective response rate (ORR) of 64 percent, compared to 36 percent with chemotherapy alone.
Data from MARIPOSA-2 study also showed that amivantamab in combination with chemotherapy demonstrates intracranial activity, critical for a disease where nearly 30 percent of patients develop brain metastases. Amivantamab plus chemotherapy reduced the risk of intracranial progression or death by 45 percent compared to chemotherapy alone, with a median intracranial progression-free survival of 12.5 versus 8.3 months (HR=0.55; 95 percent CI, 0.38–0.79).
The safety profile of amivantamab plus chemotherapy was demonstrated to be consistent with that of its individual components. Adverse events (AEs) of Grade 3 or higher, mainly due to haematologic toxicities, were reported by 72 percent of patients treated with amivantamab plus chemotherapy, and 48 percent with chemotherapy alone. The most common Grade 3 or higher AEs included neutropenia, thrombocytopenia, anaemia, and leukopenia. Grade 3 or 4 bleeding events were seen in one percent of patients treated with amivantamab plus chemotherapy, and in no patients with chemotherapy. Serious treatment-emergent AEs (TEAEs) were observed in 32 percent of patients treated with amivantamab plus chemotherapy and 20 percent with chemotherapy. Infusion-related reactions in the amivantamab plus chemotherapy arm were 58 percent (all grades). Treatment-related AEs leading to death were infrequent in all arms (2 percent vs. 1 percent) in the amivantamab plus chemotherapy and chemotherapy alone arms respectively.
Today's approval marks further positive progress in our mission to transform the treatment landscape for people living with lung cancer. This latest marketing authorisation for amivantamab underscores our commitment to advancing a robust lung cancer portfolio and redefining standards of care through precision medicine approaches."
Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Johnson & Johnson Innovative Medicine
Results from MARIPOSA-2 were presented during a Presidential Symposium at the European Society for Medical Oncology (ESMO) 2023 Congress and simultaneously published in the Annals of Oncology.
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