FDA Approves Once-Monthly SC Amivantamab Dosing in EGFR-Mutated NSCLC

The FDA has approved a new, simplified monthly subcutaneous (SC) dosing schedule for amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; Johnson & Johnson) for the treatment of patients with non–small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations.¹

Once-Monthly Dosing Simplifies Care While Maintaining Safety and Efficacy

With this approval, patients can transition from biweekly to once-monthly dosing as early as week 5 of treatment. The updated schedule further streamlines care delivery and offers greater convenience, according to Danny Nguyen, MD, assistant clinical professor at City of Hope.

“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” Nguyen said in a news release. “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.”

The approval was supported by findings from the phase 2 PALOMA-2 study (NCT05498428), presented this past September at the World Conference on Lung Cancer (WCLC) in Barcelona, Spain, by Susan Scott, MD, a thoracic medical oncologist at Johns Hopkins Kimmel Comprehensive Cancer Center.² The multicohort study evaluated the efficacy, pharmacokinetics, and safety of SC amivantamab in combination with lazertinib in treatment-naïve patients with advanced NSCLC harboring EGFR Ex19del or L858R mutations.

As of the October 24, 2024, data cutoff, 77 participants in cohort 5 received SC amivantamab coformulated with hyaluronidase via abdominal injection. Dosing was administered weekly during the first 4 weeks (600 mg for patients weighing less than 80 kg; 2240 mg for 80 kg or more), followed by once-every-4-weeks (Q4W) maintenance dosing (3520 mg or 4640 mg, respectively). Meanwhile, lazertinib 240 mg was administered orally once daily.

Although the median duration of response, progression-free survival, and overall survival were not yet estimable at the time of data cutoff, the researchers reported high efficacy with the Q4W regimen. The investigator-assessed objective response rate (ORR) was 82% (95% CI, 71%-90%), and independent central review reported an ORR of 87% (95% CI, 77%-94%). The median time to response was 8.1 weeks (range, 7.0-16.5), consistent with expectations for targeted therapy in this population.

At 6.5 months of follow-up, 87% of participants remained on treatment, suggesting durable disease control. Additionally, the regimen was generally well tolerated, with no new safety signals observed. Administration-related reactions occurred in 12% of participants, with only 1 grade 3 or higher event, substantially lower than rates typically observed with intravenous (IV) administration.

“SC amivantamab dosed once a month offers a less burdensome treatment option without compromising efficacy,” Scott said at WCLC. “These data support the potential for Q4W administration to enhance quality of life for patients with EGFR-mutant NSCLC.”

Initial SC Approval Represents Significant Step Forward in NSCLC Care

This new dosing schedule follows the FDA’s December approval of the biweekly SC administration of a fixed combination of amivantamab and recombinant human hyaluronidase in this population.³ That approval was based on results from the phase 3 PALOMA-3 study (NCT0538869), presented at the 2024 American Society of Clinical Oncology Annual Meeting. The investigators concluded that SC amivantamab maintained efficacy, improved patient and provider experience, and substantially reduced infusion-related reactions compared with the IV formulation.

In an interview with The American Journal of Managed Care^® (AJMC^®), Martin Dietrich, MD, PhD, of Cancer Care Centers of Brevard and the University of Central Florida, described the initial SC approval as a “significant step forward” for NSCLC treatment.⁴

"...By having a slower onset of the antibody via SC application, we actually bypass the vast majority of infusion-related reactions, making the treatment a lot easier for patients and for the infusion area, safer, and also more quickly done," he said.

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. February 17, 2026. Accessed February 17, 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
2. Hippensteele A. PALOMA-2 trial supports SC amivantamab Q4W as a patient-centered alternative to IV therapy. AJMC. September 8, 2025. Accessed February 17, 2026. https://www.ajmc.com/view/paloma-2-trial-supports-sc-amivantamab-q4w-as-a-patient-centered-alternative-to-iv-therapy
3. McCormick B. FDA approval of subcutaneous amivantamab offers faster, safer option for EGFR-mutated NSCLC. AJMC. December 18, 2025. Accessed February 17, 2026. https://www.ajmc.com/view/fda-approval-of-subcutaneous-amivantamab-offers-faster-safer-option-for-egfr-mutated-nsclc
4. Bonavitacola J. FDA approval of subcutaneous amivantamab is significant step forward in NSCLC: Martin Dietrich, MD, PhD. AJMC. December 18, 2025. Accessed February 17, 2026. https://www.ajmc.com/view/fda-approval-of-subcutaneous-amivantamab-is-significant-step-forward-in-nsclc-martin-dietrich-md-phd