FDA Clears Amivantamab/Chemotherapy Combo in EGFR-Mutant NSCLC
The approval of amivantamab plus carboplatin and pemetrexed is supported by data from the phase 3 MARIPOSA-2 trial.
3D rendered medical illustration of male anatomy with lung cancer: ©Sebastian Kaulitzki- stock.adobe.com
- The FDA approved amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed for the treatment of locally advanced or metastatic non–small cell lung cancer (NSCLC) with EGFR exon 19 deletions or exon 21 L858R substitution mutations.
- This indication is for patients whose disease has progressed following treatment with an EGFR tyrosine kinase inhibitor (TKI).
- The phase 3 MARIPOSA-2 trial (NCT04988295) supports this approval.
Amivantamab and carboplatin/pemetrexed chemotherapy is now an FDA-approved combination for the treatment of locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations that has progressed following an EGFR TKI.1
Data from the MARIPOSA-2 trial support this approval. Here, 657 patients who experienced disease progression on or after treatment with osimertinib (Tagrisso) were randomized 1:2:2 to receive amivantamab plus chemotherapy, chemotherapy, or amivantamab as part of another combination regimen.
The primary end point was progression-free survival (PFS) assessed by blinded independent central review. The median PFS was 6.3 months (95% CI, 5.6-8.4) with amivantamab and chemotherapy vs 4.2 months (95% CI, 4.0-4.4) in the chemotherapy arm (HR, 0.48; 95% CI, 0.36-0.64; P<.0001. The overall response rate, a key secondary end point, was 53% (95% CI, 44%-62%) in the amivantamab/chemotherapy arm vs 29% (95% CI, 23%-35%) in the chemotherapy arm (P <.0001).
Regarding overall survival (OS), there was no statistically significant difference between the 2 arms, with a stratified OS HR of 0.73 (95% CI, 0.54-0.99; P =.039).
At the 2024 ESMO Congress, longer term follow-up results from MARIPOSA-2 were presented. Patients assigned amivantamab plus chemotherapy had a median OS of 17.7 months (95% CI, 16.0-22.4) compared with 15.3 months (95% CI, 13.7-16.8) in patients assigned chemotherapy alone. OS was 50% for the amivantamab plus chemotherapy group vs 40% in the chemotherapy alone group.2
“Indeed, amivantamab’s multi-targeted mechanism of action and immune cell-directed activity, combined with chemotherapy's nonspecific antitumor effects, likely contributes to this observed durability,” Sanjay Popat, BSc, MBBS, FRCP, PhD, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research in London, said during the presentation of the data.
Adverse effects occurring in 20% or more of patients were rash, infusion-related reactions, fatigue, nail toxicity, nausea, constipation, edema, stomatitis, decreased appetite, musculoskeletal pain, vomiting, and COVID-19 infection.1
On August 20, 2024, the FDA approved the combination of amivantamab and lazertinib (Lazcluze) for the first-line treatment of EGFR-mutated NSCLC with exon 19 deletions or exon 21 L858R substitution mutations.3
