EMA Committee recommends Rybrevant in combo with chemotherapy for adult patients with lung cancer after failure of prior therapy
Beerse: Janssen-Cilag International NV, a Johnson & Johnson company, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended the approval of a Type II extension of indication for RYBREVANT (amivantamab) in combination with chemotherapy (carboplatin and pemetrexed), for the treatment of adult patients 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).
“Resistance mechanisms after disease progression on osimertinib are diverse and polyclonal, with up to half being EGFR and MET-based alterations. There are no targeted therapies approved for the post-osimertinib setting, and outcomes with the current standard of care, platinum-based chemotherapy, are poor,” said Antonio Passaro, M.D., Ph.D., Medical Oncologist, Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy*. “The combination of amivantamab and chemotherapy offers renewed hope and a new standard of care for these patients, with improvements observed in response rates, progression-free survival, and intracranial efficacy, even in patients with previously untreated brain metastases.”
“EGFR gene mutations are the most common actionable oncogenic mutations in NSCLC, with ex19del or L858R mutations representing up to 90 percent of all EGFR mutations,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “At Johnson & Johnson, our dedication to transforming the treatment of lung cancer with innovative therapies is unwavering, and we are proud to take another step forward for patients in need of new, targeted treatment options.”
The CHMP recommendation for amivantamab is supported by data from the Phase 3 MARIPOSA-2 (NCT04988295) study, 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.
The data from MARIPOSA-2 also showed that amivantamab combination regimens may provide intracranial activity, critical for a disease where nearly 30 percent of patients develop brain metastases. Specifically, 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; P=0.001).
The safety profile of amivantamab plus chemotherapy is consistent with that of its individual components.
“The positive CHMP opinion is welcome news and demonstrates the results of our deep commitment to transforming outcomes for patients with NSCLC,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumours, Johnson & Johnson Innovative Medicine. “Amivantamab has already shown positive outcomes in treating patients with other EGFR mutations, and we now look forward to the next steps in making it available to further patients with common EGFR mutations after progression on osimertinib”
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.
