On March 1, the FDA approved the monoclonal bispecific anti–EGFR-MET antibody amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for the first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test.
The FDA also granted traditional approval to amivantamab for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. The FDA previously granted accelerated approval for this indication.
PAPILLON
Efficacy was evaluated in PAPILLON (ClinicalTrials.gov identifier NCT04538664), a randomized, open-label multicenter trial of 308 patients with EGFR exon 20 insertion mutations. Patients were randomly assigned 1:1 to receive amivantamab with carboplatin and pemetrexed or carboplatin and pemetrexed.
The major efficacy outcome measure was progression-free survival as assessed by blinded independent central review, with overall survival as a key secondary outcome measure. Amivantamab plus carboplatin and pemetrexed demonstrated a statistically significant improvement in progression-free survival compared with carboplatin and pemetrexed, with a hazard ratio of 0.40 (95% confidence interval [CI] = 0.30–0.53, P < .0001). The median progression-free survival was 11.4 months (95% CI = 9.8–13.7 months) and 6.7 months (95% CI = 5.6–7.3 months) in the respective arms. While overall survival results were immature at the current analysis, with 44% of prespecified deaths for the final analysis reported, no trend toward a detriment was observed.
The most common adverse reactions reported in patients taking amivantamab (≥ 20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19 infection, diarrhea, and vomiting.
More About the Approval
The recommended amivantamab dose is based on body weight; see the prescribing information for specific dosage information.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, the FDA collaborated with the Brazilian Health Regulatory Agency and Health Canada. The application reviews are ongoing at the other regulatory agencies.
This review used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 weeks ahead of the FDA goal date.
This application was granted Priority Review.
