FDA Approves Simplified Once-Monthly Amivantamab Plus Hyaluronidase Regimen for First-Line EGFR-Mutated Advanced NSCLC
Key Clinical Summary:
- The FDA has approved a once-monthly dosing schedule for subcutaneous amivantamab plus hyaluronidase in combination with lazertinib for the first-line treatment of EGFR-mutated advanced non-small cell lung cancer, supported by data from the phase 2 PALOMA-2 study.
- Monthly dosing demonstrated high objective response rates with pharmacokinetic exposure comparable to bi-weekly subcutaneous and historical intravenous administration. Administration-related reactions were markedly reduced compared with intravenous delivery and were consistent with the bi-weekly subcutaneous schedule, with no new safety signals identified.
- This approval further simplifies administration of a regimen associated with improved survival outcomes, offering a more convenient treatment schedule while maintaining efficacy and a manageable safety profile in EGFR-mutated advanced non-small cell lung cancer.
On February 17, 2026, the US Food and Drug Administration (FDA) has approved a new, simplified once-monthly dosing schedule for amivantamab plus hyaluronidase when administered in combination with lazertinib for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC). This approval was based on results from the PALOMA-2 trial.
In this open-label study, 77 patients received 1600 mg (2240 mg for patients ≥80 kg) of amivantamab once weekly for the first 4 weeks, followed by 3520 mg (4640 mg for patients ≥80 kg) once monthly thereafter, with 240 mg of once daily lazertinib. The primary end point was investigator-assessed objective response rate (ORR). Key secondary end points included ORR by blinded independent central review, time to response, clinical benefit rate, and safety.
At a median follow-up of 6.5 months, confirmed ORR was 79% by investigator assessment and 83% by blinded independent central review. The median time to response was 8.1 weeks, and the confirmed clinical benefit rate was 97%. At the time of analysis, 87% of patients remained on protocol therapy and 93% of responses were ongoing.
No new safety signals were identified. The most common grade ≥3 treatment-emergent adverse events occurring in ≥20% of patients included paronychia (5%), rash (12%), dermatitis acneiform (8%), stomatitis (4%), pruritus (1%), diarrhea (3%), hypoalbuminemia (5%), increased ALT (4%), and increased AST (1%). Treatment-emergent adverse events led to treatment discontinuation in 8% of patients. ARR rate was 12% (1% grade ≥3) with 78% occurring at first injection.
“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” stated principal investigator Danny Nguyen, MD, City of Hope, Huntington Beach, California. “With a flexible schedule that reduces time in the clinic, patients may be able to stay on therapy longer and free up time to focus on the moments that matter most.”
This approval follows the recent FDA approval of subcutaneous amivantamab plus hyaluronidase based on results from the PALOMA-3 trial and allows patients to switch to monthly dosing as early as week 5.
Sources:
- Johnson and Johnson. FDA approves RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as the only EGFR-targeted therapy that can be administered once a month. Accessed February 18, 2026. https://www.jnj.com/media-center/press-releases/fda-approves-rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-as-the-only-egfr-targeted-therapy-that-can-be-administered-once-a-month
- Scott SC, Mourão Dias J, Liu B, et al. PALOMA-2: Subcutaneous amivantamab administered every 4 weeks plus lazertinib in first-line EGFR-mutated advanced NSCLC. Presented at IASLC 2025 WCLC. September 6-9, 2025; Barcelona, Spain.
