FDA OKs Once-Monthly Subcutaneous Amivantamab Dose in EGFR+ NSCLC

The FDA has approved a once-monthly dosing schedule for subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) when combined with lazertinib (Lazcluze) as a frontline treatment for patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to a press release from the developer, Johnson & Johnson.¹

The press release noted that monthly dosing with subcutaneous amivantamab may produce similar outcomes as the previously approved biweekly dosing schedule for the agent. The FDA originally approved subcutaneous amivantamab plus lazertinib for this NSCLC population in December 2025 based on data from the phase 3 PALOMA-3 trial (NCT05388669).²

“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” Danny Nguyen, MD, an assistant clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, as well as principal investigator for the PALOMA-3 trial and MARIPOSA trial (NCT04487080), stated in the press release.¹ “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.”

At the time of the original FDA approval, topline data from the PALOMA-3 study showed that subcutaneous amivantamab reached both coprimary pharmacokinetic end points based on amivantamab levels in the blood. Other findings showed that the subcutaneous formulation of the agent could reduce administration time from several hours to 5 minutes with an approximately 5-fold reduction in the risk of administration-related reactions at 13% vs 66% with intravenous amivantamab. Additionally, venous thromboembolism events were noted in 11% of the subcutaneous arm and 18% of the intravenous arm.

Previous data presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting showed that subcutaneous amivantamab improved duration of response (DOR), progression-free survival (PFS), and overall survival (OS) vs the intravenous formulation of the agent.³ At 12 months, the OS rates were 65% with subcutaneous amivantamab vs 51% with its intravenous formulation (HR, 0.62; 95% CI, 0.42-0.92; P = .02).

Patients in the open-label phase 3 PALOMA-3 trial were randomly assigned to receive amivantamab intravenously or subcutaneously in combination with lazertinib at 240 mg orally once daily.⁴ In the subcutaneous arm, patients received amivantamab co-formulated with recombinant human hyaluronidase at 1600 or 2240 mg based on individual body weight. Those in the intravenous arm received amivantamab at 1050 or 1400 mg depending on body weight.

The trial’s primary end points included observed serum concentration of amivantamab at steady state and area under the concentration time curve of amivantamab. Secondary end points included ORR, PFS, DOR, time to response, adverse effects, clinical laboratory abnormalities, and infusion-related reactions.

Patients 18 years and older with histologically or cytologically confirmed advanced or metastatic NSCLC harboring EGFR exon 19 deletions or exon 21 L858R mutations, progression on or after osimertinib (Tagrisso) or another approved third-generation EGFR tyrosine kinase inhibitor and platinum-containing chemotherapy were eligible for enrollment on the trial. Other eligibility criteria included having at least 1 measurable lesion based on RECIST v1.1 guidelines and an ECOG performance status of 0 or 1.

“This latest milestone represents the culmination of our unwavering efforts and commitment to fundamentally redefine the way we treat patients with EGFR-mutated [NSCLC]. Building on unmatched [OS] and regimens that support proactive [adverse] effect management, this once-monthly injection now delivers the simplest and fastest combination therapy for patients with EGFR-mutated [NSCLC],” Mahadi Baig, MD, MHCM, vice president of US Medical Affairs at Johnson & Johnson, said in the press release.¹

References

1. FDA approves RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) as the only EGFR-targeted therapy that can be administered once a month. News release. Johnson & Johnson. February 17, 2026. Accessed February 17, 2026. https://tinyurl.com/5t5d7nar
2. U.S. FDA approval of RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) enables the simplest, shortest administration time for a first-line combination regimen when combined with LAZCLUZE® (lazertinib). News release. Johnson & Johnson. December 17, 2025. Accessed February 17, 2026. https://tinyurl.com/2wt6j6be
3. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605. doi: 10.1200/JCO.24.01001
4. A study of lazertinib with subcutaneous amivantamab compared with intravenous amivantamab in participants with epidermal growth factor receptor (EGFR)-mutated advanced or metastatic non-small cell lung cancer (PALOMA-3). ClinicalTrials.gov. Updated February 2, 2026. Accessed February 17, 2026. https://tinyurl.com/yvdvr62c