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 amivantamab (Rybrevant) in combination with carboplatin and pemetrexed chemotherapy, according to an announcement from Janssen-Cilag International NV, a Johnson & Johnson company.
The recommended extension of indication for the treatment for adults with advanced non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions (ex19del) or exon 21 L858R substitution (L858R) mutations after patients experience failure of prior therapy, including an EGFR tyrosine kinase inhibitor.
Amivantamab is a fully human EGFR-MET bispecific antibody. The European Commission previously granted conditional marketing authorization of amivantamab in December 2021 as a treatment for advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum-based therapy.
“Today’s positive CHMP opinion is welcome news and demonstrates the results of our deep commitment to transforming outcomes for patients with NSCLC,” Kiran Patel, MD, Vice President of Clinical Development in Solid Tumours at Johnson & Johnson Innovative Medicine, said in a statement. “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.”
The CHMP recommendation for amivantamab is supported by data from the phase 3 MARIPOSA-2 study, which evaluated the efficacy and safety 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, officials said in the release.
The arm of MARIPOSA-2 that evaluated amivantamab plus chemotherapy met its primary end point, reducing the risk of disease progression or death by 52%. The median progression-free survival (PFS) was 6.3 months in those receiving amivantamab plus chemotherapy, compared with 4.2 months in those receiving chemotherapy alone (hazard ratio [HR], 0.48; P<.001).
A medical oncologist weighed in on what the recent regulatory action means for patients and clinicians.
“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,” Antonio Passaro, MD, PhD, a medical oncologist in the Division of Thoracic Oncology at the European Institute of Oncology, said in a statement. “The combination of amivantamab and chemotherapy offers renewed hope and a new standard of care for these patients, with improvements observed in response rates, [PFS], and intracranial efficacy, even in patients with previously untreated brain metastases.”
The combination therapy also showed an objective response rate (ORR) of 64%, nearly double the ORR of 36% observed in the patients receiving chemotherapy alone. In addition, the MARIPOSA-2 study showed that amivantamab plus chemotherapy reduced the risk of intracranial progression or death by 45% compared with chemotherapy alone, with a median intracranial PFS of 12.5 months in those receiving the combination, significantly higher than the median intracranial PFS of 8.3 months in those receiving chemotherapy alone (HR, 0.55; P=.001). These results show that amivantamab combination regimens “may provide intracranial activity,” which is “critical for a disease where nearly 30% of patients develop brain metastases,” officials said in the announcement.
The safety profile of amivantamab plus chemotherapy is “consistent with that of its individual components,” according to officials. Adverse events (AEs) of grade 3 or higher, “mainly due to hematologic toxicities,” were reported by 72% of patients treated with amivantamab plus chemotherapy and 48% of those who received chemotherapy alone.
The most common AEs of grade 3 or higher included neutropenia, thrombocytopenia, anemia, and leukopenia. Serious treatment-emergent AEs were reported by 32% of patients treated with amivantamab plus chemotherapy and 20% of those receiving chemotherapy alone. Among the patients receiving amivantamab plus chemotherapy, infusion-related reactions occurred in 58%. Treatment-related AEs leading to death occurred in 2% of patients receiving amivantamab plus chemotherapy and 1% of those receiving chemotherapy alone.
In line with EMA regulations for new medicines, amivantamab is subject to additional monitoring, officials said in the announcement.
Source: Johnson & Johnson
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