Site Editor
Gregory J. Riely, MD, PhD
Gregory J. Riely, MD, PhD
Posted: Monday, September 23, 2024
On September 19, the U.S. Food and Drug Administration (FDA) approved the bispecific antibody amivantamab-vmjw (Rybrevant) with carboplatin and pemetrexed for adults with locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations. They had to have disease progression on or after treatment with an EGFR tyrosine kinase inhibitor.
Efficacy was evaluated in the phase III MARIPOSA-2 (ClinicalTrials.gov identifier NCT04988295), a randomized, open-label, multicenter trial in 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations and disease progression on or after osimertinib treatment. Patients were randomly assigned (1:2:2) to receive amivantamab with carboplatin and pemetrexed (amivantamab + CP), carboplatin and pemetrexed (CP), or amivantamab as part of another combination regimen.
Median progression-free survival (the major efficacy outcome measure) was 6.3 months (95% confidence interval [CI] = 5.6–8.4 months) with amivantamab plus CP and 4.2 months (95% CI = 4.0–4.4 months) with CP alone (hazard ratio = 0.48 [95% CI = 0.36–0.64], P < .0001). The confirmed overall response rate (a secondary outcome measure) was 53% (95% CI = 44%–62%) with amivantamab plus CP and 29% (95% CI = 23%–35%) with CP alone (P < .0001). At the prespecified second interim analysis of overall survival (another secondary outcome measure), with 85% of the deaths needed for the final analysis, there was no statistically significant difference between the treatment arms. The stratified overall survival hazard ratio was 0.73 (95% CI = 0.54–0.99).
The most common adverse reactions with amivantamab in this trial (≥ 20%) were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.
The recommended amivantamab-vmjw dose is based on baseline body weight. For more detailed information on dosing, see the prescribing information at Drugs@FDA.
U.S. Food and Drug Administration
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