FDA approves amivantamab-vmjw for EGFR exon 20 insertion-mutated non-small cell lung cancer indications

Regulatory approval: On March 1, 2024, the FDA approved amivantamab-vmjw (Rybrevant) plus carboplatin and pemetrexed for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations (FDA-approved test required). The FDA also granted traditional approval for amivantamab-vmjw monotherapy in adults with the same biomarker whose disease progressed on/after platinum-based chemotherapy, converting a prior accelerated approval. The first-line approval was supported by PAPILLON, showing improved PFS vs chemotherapy alone.

FDA regulatory approval (March 1, 2024)

The US FDA approved amivantamab-vmjw (Rybrevant; Janssen Biotech, Inc.) with carboplatin and pemetrexed for 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 amivantamab-vmjw for adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations (FDA-approved test) whose disease has progressed on or after platinum-based chemotherapy; this indication had previously received accelerated approval.

Key evidence

Efficacy for the first-line regimen was evaluated in PAPILLON (NCT04538664), a randomized, open-label, multicenter trial (n=308) in patients with EGFR exon 20 insertion mutations, randomized 1:1 to amivantamab-vmjw + carboplatin/pemetrexed vs carboplatin/pemetrexed.

  • Primary endpoint: PFS by BICR (OS key secondary).
  • PFS: HR 0.40 (95% CI, 0.30–0.53; p<0.0001); median 11.4 months vs 6.7 months, respectively.
  • OS: results immature (44% of pre-specified deaths); no trend toward detriment reported.

Safety

Common adverse reactions (≥20%) included rash, nail toxicity, stomatitis, infusion-related reaction, fatigue, edema, constipation, decreased appetite, nausea, COVID-19, diarrhea, and vomiting.

The review used Project Orbis and RTOR; partner agency reviews were reported as ongoing.

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