FDA Approves Amivantamab Plus Chemo Combo for Advanced NSCLC With EGFR Exon 20 Insertion Mutations

FDA Approves Amivantamab Plus Chemo Combo for Advanced NSCLC With EGFR Exon 20 Insertion Mutations

The FDA approved amivantamab-vmjw (Rybrevant) in combination with carboplatin and pemetrexed for the first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.

In addition, a traditional approval was also granted by the FDA to amivantamab for adult patients with locally advanced or metastatic NSCLC with EGFR insertion mutations with disease progression on or after platinum-based chemotherapy, according to an alert from the agency.

The FDA approval was based on findings from the PAPILLON (NCT04538664) trial, which analyzed data from 308 patients with EGFR exon 20 insertion mutations. In this randomized, open-label, multicenter trial, patients were randomized 1:1 to receive either amivantamab with carboplatin and pemetrexed or the chemotherapy combination alone.

The major efficacy outcome measure in the PAPILLON trial was progression-free survival (PFS) assessed by blinded independent central review, with a secondary outcome measure of overall survival (OS).

Compared with carboplatin and pemetrexed, amivantamab plus the chemotherapy combination demonstrated a statistically significant improvement in PFS (HR = 0.40; 95% CI, 0.30-0.53; P < .0001). The median PFS was 11.4 months (95% CI, 9.8-13.7) in the amivantamab plus chemotherapy arm compared with 6.7 months (95% CI, 5.6-7.3) in the chemotherapy combination-only arm.

Results regarding OS were immature at the current analysis, according to the FDA alert, with 44% of prespecified deaths reported for the final analysis. Researchers noted that there was no trend toward a detriment.

The most common adverse reactions, occurring in at least 20% of patients, include nail toxicity, rash, infusion-related reaction, stomatitis, edema, fatigue, decreased appetite, constipation, COVID-19, nausea, vomiting, and diarrhea.

The FDA noted that the recommended dose of amivantamab is based on body weight.

Of note, amivantamab was previously granted accelerated approval by the FDA for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations with progression on or after platinum-based chemotherapy.

Reference

FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications. News release. FDA. March 1, 2024. Accessed March 1, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-egfr-exon-20-insertion-mutated-non-small-cell-lung-cancer-indications