CHMP Backs RYBREVANT® With Chemotherapy After Previous Treatment Failures

Janssen-Cilag International NV, part of Johnson & Johnson, announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) has recommended approval for a new use of RYBREVANT®▼ (amivantamab). This approval would allow RYBREVANT®, combined with chemotherapy drugs carboplatin and pemetrexed, to treat adult patients with advanced non-small cell lung cancer (NSCLC) who have specific EGFR mutations (Exon 19 deletions or Exon 21 L858R substitutions) and have previously been treated with an EGFR tyrosine kinase inhibitor (TKI).

Antonio Passaro, M.D., Ph.D., Medical Oncologist, Division of Thoracic Oncology at the European Institute of Oncology in Milan, Italy, “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. 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.”

Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine, also commented “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. 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's recommendation for amivantamab is based on results from the Phase 3 MARIPOSA-2 (NCT04988295) study, which assessed the drug's efficacy and safety in combination with chemotherapy for patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC who experienced disease progression following osimertinib treatment.

The study revealed that the combination of amivantamab and chemotherapy significantly reduced the risk of disease progression or death by 52% 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% confidence interval [CI], 0.36–0.64; P<0.001). Furthermore, the combination therapy demonstrated an objective response rate (ORR) of 64%, compared to 36% with chemotherapy alone.

The MARIPOSA-2 study data indicate that combining amivantamab with chemotherapy may offer intracranial benefits, which is crucial since nearly 30% of NSCLC patients develop brain metastases. Specifically, the combination reduced the risk of intracranial progression or death by 45% compared to chemotherapy alone, achieving a median intracranial progression-free survival of 12.5 months versus 8.3 months (HR=0.55; 95% CI, 0.38–0.79; P=0.001).

The safety profile of the amivantamab and chemotherapy combination aligns with the known effects of its individual components. Grade 3 or higher adverse events (AEs), primarily hematologic toxicities, were observed in 72% of patients receiving the combination treatment, compared to 48% with chemotherapy alone.

The most frequent severe AEs included neutropenia, thrombocytopenia, anemia, and leukopenia. Grade 3 or 4 bleeding events occurred in 1% of patients treated with the combination, but none in the chemotherapy-only group. Serious treatment-emergent AEs were seen in 32% of the combination group and 20% of the chemotherapy group. Infusion-related reactions were reported in 58% of patients in the combination arm (all grades). Treatment-related AEs leading to death were rare, occurring in 2% of the combination group and 1% of the chemotherapy-only group.