FDA Approves Monthly Dosing for Johnson & Johnson's Rybrevant Faspro in NSCLC

The FDA has approved a once-monthly subcutaneous injection dosing schedule for amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for the first-line treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer. The approval builds upon the drug's previous biweekly dosing schedule approved in December 2025, offering patients a more convenient treatment option with comparable efficacy and safety.

The new monthly dosing approval was based on findings from the PALOMA-2 trial showing that monthly injections in combination with lazertinib delivered high objective response rates — 82% and 87% by investigator and independent central review, respectively — in previously untreated EGFR-mutated advanced NSCLC. The trial also showed a significant reduction in administration-related reactions when compared with rates seen historically with intravenous administration and comparable ARRs to those seen with biweekly subcutaneous injections.

Administration-related reactions with monthly versus biweekly dosing were 12% and 13%, respectively, and were fivefold lower versus historical data for IV administration. The safety profile of monthly dosing is comparable to that seen with biweekly dosing, with most adverse events related to EGFR/MET oncogene inhibition. No new safety signals were observed in PALOMA-2, and only 8% of patients discontinued injections due to treatment-related adverse events.

Mean plasma concentrations were consistent with IV and biweekly subcutaneous dosing, suggesting pharmacokinetic comparability across the dosing regimens. With this newly approved monthly dosing schedule, patients are able to transition to monthly dosing as early as Week 5, reducing time in the clinic.

At the moment, Rybrevant is the only drug approved in the front-line setting for EGFR-mutated NSCLC with exon 20 insertion mutations, administered intravenously in combination with chemotherapy. The drug first demonstrated efficacy in the PALOMA-3 trial, which supported its initial approval.

The approval comes as other companies are developing treatments for this challenging patient population. Dizal Pharmaceutical's Zegfrovy has taken the EGFR inhibitor class into new territory after hitting the mark in a phase 3 trial as a first-line treatment for NSCLC with EGFR exon 20 insertion mutations. The readout of the WU-KONG28 study showed a statistically significant improvement in progression-free survival with Zegfrovy monotherapy over a platinum-based chemotherapy regimen, offering the prospect of becoming the first "oral, once daily, chemo-free, targeted therapy" for these patients.

Orally-active, tyrosine kinase inhibitor-based EGFR drugs, including AstraZeneca's market-leading Tagrisso, have struggled to show efficacy against this type and are used mainly to treat tumours with exon 19 and 21 mutations. NSCLC driven by exon 20 mutations tend to carry a worse prognosis and shorter survival times. Zegfrovy claimed accelerated approval from the FDA last July as a second-line or later therapy for NSCLC with EGFR exon 20 insertions in patients whose cancer has progressed on or after platinum-based chemo, and has also been cleared for this indication in China.

Other oral drugs are being tested as first-line therapy for NSCLC patients with EGFR exon 20 insertions, including ArriVent Biopharma's furmonertinib, which is in the phase 3 FURVENT trial and due to generate results in the first half of this year.