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Gregory J. Riely, MD, PhD


FDA Approves Bispecific Antibody Plus Chemotherapy for EGFR Exon 20 Insertion–Mutated NSCLC

By: JNCCN 360 Staff
Posted: Monday, March 4, 2024

On March 1, the U.S. Food and Drug Administration (FDA) approved amivantamab-vmjw (Rybrevant) with carboplatin and pemetrexed in the first-line treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. The FDA also granted traditional approval to this bispecific antibody for adults 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 had granted accelerated approval to this agent for this indication in May 2021.

Efficacy was evaluated in the phase III randomized PAPILLON 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. Although overall survival results were immature at the time of 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 to amivantamab in this trial (≥ 20%) were rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19 infection, diarrhea, and vomiting.

The recommended dose of amivantamab is based on body weight. See full prescribing information for details on specific dosage.

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