FDA Approves Simplified Monthly Dosing Schedule for Subcutaneous Amivantamab Plus Hyaluronidase
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 (NSCLC), based on findings from the phase 2 PALOMA-2 trial.
- Once-monthly dosing produced high objective response rates with pharmacokinetic exposure comparable to biweekly subcutaneous and historical intravenous administration. Administration-related reactions remained infrequent, no new safety signals were identified, and treatment discontinuation rates were low.
- This approval offers a more convenient dosing schedule while maintaining the efficacy and safety profile of subcutaneous amivantamab plus hyaluronidase, further simplifying first-line treatment for patients with EGFR-mutated advanced NSCLC.
The US Food and Drug Administration (FDA) has approved a once-monthly dosing schedule for subcutaneous amivantamab plus hyaluronidase in combination with lazertinib for the first-line treatment of patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC). The approval was supported by findings from the phase 2 PALOMA-2 trial.
In this open-label trial, 77 patients received 1600 mg of amivantamab plus hyaluronidase (2240 mg for patients weighing ≥80 kg) once weekly for the first 4 weeks, followed by 3520 mg (4640 mg for patients weighing ≥80 kg) once monthly beginning at week 5, in combination 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, the confirmed ORR was 79% by investigator assessment and 83% by blinded independent central review. 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 study treatment, and 93% of responses were ongoing.
No new safety signals were identified. Administration-related reactions occurred in 12% of patients, with grade ≥3 events reported in 1% of patients; 78% of reactions occurred with the first injection. Treatment-emergent adverse events led to treatment discontinuation in 8% of patients. The most common grade ≥3 treatment-emergent adverse events included rash (12%), dermatitis acneiform (8%), paronychia (5%), hypoalbuminemia (5%), stomatitis (4%), increased alanine aminotransferase (4%), diarrhea (3%), pruritus (1%), and increased aspartate aminotransferase (1%).
“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” stated principal investigator Danny Nguyen, MD, of 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.”
The approval follows the FDA approval of subcutaneous amivantamab plus hyaluronidase based on the phase 3 PALOMA-3 trial and allows eligible patients to transition to once-monthly dosing beginning at 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.
