FDA OKs Subcutaneous Amivantamab Across All NSCLC Indications

The FDA has approved the use of subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) for use in all approved indications for intravenous amivantamab, according to a press release from Johnson & Johnson, the developer of the agent.¹

Findings from the phase 3 PALOMA-3 trial (NCT05388669) confirmed the subcutaneous formulation delivers noninferior levels of amivantamab to patients as the intravenous formulation, meeting primary pharmacokinetic end points of trough concentrations (C_trough) and area under the curve (AUC). Further, overall survival (OS) was significantly higher in patients receiving subcutaneous treatment. Data were shared at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.

The geometric mean ratios of C_trough for subcutaneous to intravenous therapy were 1.15 (90% CI, 1.04-1.26) at cycle 2 day 1 and 1.42 (90% CI, 1.27-1.61) at cycle 4 day 1, and cycle 2 AUC days 1 to 15 was 1.03 (90% CI, 0.98-1.09).²

The objective response rate (ORR) was 30% (95% CI, 24%-37%) vs 33% (95% CI, 26%-39%) in subcutaneous and intravenous groups, respectively (relative risk, 0.92; 95% CI, 0.70-1.23). These findings met noninferiority criteria by maintaining at least 60% ORR in the intravenous group.

Median time to response was 1.5 months (range, 1.2-6.9) in patients receiving subcutaneous therapy and 1.5 months (range, 1.2-9.9) in those receiving intravenous therapy. Median duration of response (DOR) was 11.2 months (95% CI, 6.1-not estimable [NE]) vs 8.3 months (95% CI, 5.4-NE), respectively. Of responders in each group, 29% and 14%, respectively, had a DOR of at least 6 months.

Subcutaneous amivantamab reduced the risk of death by 38% (HR, 0.62; 95% CI, 0.42-0.92; nominal P = .02). At 6 and 12 months, 85% (95% CI, 79%-89%) and 65% (95% CI, 52%-74%) of patients were alive, respectively, in the subcutaneous arm; 75% (95% CI, 68%-80%) and 51% (95% CI, 37%-64%) were alive at these time points in the intravenous arm. In total, 43 and 62 patients in the subcutaneous and intravenous groups, respectively, died during the trial, with 81% of each arm dying due to progressive disease.

Indications and Dosing of Amivantamab

Amivantamab is approved in combination with lazertinib (Lazcluze) for the frontline treatment of adult patients with locally advanced or metastatic non–small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions or exon 21 L858R substitution mutation; in combination with carboplatin and pemetrexed for the treatment of patients in the same population whose disease has progressed on or after treatment with an EGFR tyrosine kinase inhibitor; in combination with carboplatin and pemetrexed for the frontline treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations; and as monotherapy for pretreated patients with locally advanced or metastatic NSCLC harboring EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. All indications require patient identification via an FDA-approved test.

When administering amivantamab in combination with lazertinib or as a single agent, amivantamab should be given at 1050 mg for patients weighing less than 80 kg and 1400 mg for patients weighing at least 80 kg. In combination with chemotherapy, amivantamab should be given at 1400 mg weeks 1 to 4 and at 1750 mg week 7 and beyond for patients weighing less than 80 kg, and at 1750 mg weeks 1 to 4 and 2100 mg week 7 and beyond in patients weighing at least 80 kg.

References

1. 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). Johnson & Johnson. News release. December 17, 2025. Accessed December 17, 2025. https://www.jnj.com/media-center/press-releases/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
2. 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
3. Rybrevant. Prescribing information. Johnson & Johnson; 2025. Accessed December 17, 2025. https://www.jnjlabels.com/package-insert/product-monograph/prescribing-information/RYBREVANT-pi.pdf