The recent approval by the Food and Drug Administration (FDA) of amivantamab-vmjw (Rybrevant, Janssen Biotech) marks a significant milestone in the treatment landscape for non-small cell lung cancer (NSCLC). This approval targets locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, a subgroup historically challenging to treat effectively.
The FDA has granted traditional approval to amivantamab-vmjw for adult patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations, after progression on platinum-based chemotherapy. Notably, accelerated approval was previously granted for this indication.
Image credit: Vinoth Khandelwal
Amivantamab-vmjw, a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. Amivantamab-vmjw, administered in combination with carboplatin and pemetrexed, has demonstrated efficacy in improving progression-free survival (PFS) compared to carboplatin and pemetrexed alone. The recommended dosage is weight-based, as outlined in the prescribing information.
Efficacy data was based from the PAPILLON trial (NCT04538664), involving 308 patients with EGFR exon 20 insertion mutations. The trial randomized patients to receive either amivantamab-vmjw with carboplatin and pemetrexed or carboplatin and pemetrexed alone. The primary endpoint was PFS, assessed by blinded independent central review, with overall survival (OS) as a key secondary endpoint. Amivantamab-vmjw, in combination with carboplatin and pemetrexed, demonstrated a statistically significant improvement in PFS, with a hazard ratio of 0.40 (95% CI: 0.30, 0.53; p-value < 0.0001). The median PFS was notably extended to 11.4 months compared to 6.7 months in the control arm. Common adverse reactions associated with amivantamab-vmjw include rash, nail toxicity, stomatitis, infusion-related reactions, and fatigue. Notably, the drug’s safety profile warrants monitoring and management of these adverse events.
The approval of amivantamab-vmjw represents a significant advancement in the treatment landscape for EGFR exon 20 insertion-mutated NSCLC, addressing an unmet need in this patient population. The collaboration under Project Orbis and utilization of expedited review programs underscore the FDA’s commitment to accelerating access to promising therapies for patients with serious conditions.
