FDA Grants Approval to Amivantamab With Carboplatin and Pemetrexed for Patients With NSCLC With EGFR Exon 19 Deletions or L858R Mutations

On September 19th, 2024, the US Food and Drug Administration (FDA) granted approval to amivantamab-vmjw (amivantamab) with carboplatin and pemetrexed for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations with disease progression on or following  EGFR tyrosine kinase inhibitor therapy. This approval was based on results from the MARIPOSA-2 trial.

In this randomized, open-label, multicenter trial, 657 patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations were examined for disease progression on or after receiving osimertinib. Patients were randomized on a 1 to 2 to 2 basis to receive amivantamab in addition to carboplatin and pemetrexed, carboplatin and pemetrexed, or amivantamab as part of another combination regimen.

Researchers noted the primary outcome was progression-free survival (PFS) as assessed by blinded independent central review (BICR) for the comparison between amivantamab plus carboplatin and pemetrexed, and carboplatin and pemetrexed. It was determined that overall response rate (ORR) per BICR and overall survival (OS) served as the secondary outcome measures.

Results demonstrated a median PFS of 6.3 months (95% [confidence interval] CI, 5.6 to 8.4) in the amivantamab plus carboplatin and pemetrexed cohort and 4.2 months (95% CI, 4 to 4.4) in the carboplatin and pemetrexed arm (hazard ratio [HR] 0.48; 95% CI, 0.36 to 0.64), P < 0.0001). Furthermore, the confirmed ORR was 53% (95% CI, 44 to 62) in the amivantamab plus carboplatin and pemetrexed arm and 29% (95% CI, 23 to 35) in the carboplatin and pemetrexed arm (P < 0.0001).

At the predetermined second interim analysis of OS, investigators determined there was no statistically significant difference in OS. The stratified OS HR was 0.73 (95% CI, 0.54 to 0.99). The measured safety profile noted the most common adverse events ( ≥ 20%) were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.

Source:

FDA approves amivantamab-vmjw with carboplatin and pemetrexed for non-small cell lung cancer with EGFR exon 19 deletions or L858R mutations. US Food and Drug Administration. Published online September 19, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-amivantamab-vmjw-carboplatin-and-pemetrexed-non-small-cell-lung-cancer-egfr-exon-19