FDA Approves Subcutaneous Amivantamab for EGFR-Mutated NSCLC

The FDA has approved a subcutaneous formulation of amivantamab and hyaluronidase for patients with EGFR-mutated non-small cell lung cancer across all approved indications for amivantamab. The approval, which occurred in December 2025, is based on results from the pivotal phase 3 PALOMA-3 trial showing the subcutaneous formulation offers faster treatment, fewer infusion reactions, and improved convenience compared to intravenous administration.

The phase 3 PALOMA-3 trial demonstrated that subcutaneous amivantamab combined with lazertinib had a more favorable safety profile compared with intravenous amivantamab plus lazertinib and was noninferior to the IV formulation in terms of efficacy. The subcutaneous formulation heavily decreases infusion-related reactions from 66% to 13%, with administration time reduced from about 5 hours with IV to just 5 minutes with subcutaneous injection.

One of the critical advantages is that patients now have more time away from the clinic, reducing the time toxicity of coming to the cancer center and improving quality of life, especially for younger patients who are working. The subcutaneous formulation doesn't reduce skin toxicity, but it does allow infusion-related reactions to be fewer and allows patients not to come into the cancer center as often.

Recent updates for overall survival data from the phase 3 MARIPOSA trial further support the use of amivantamab plus lazertinib over osimertinib monotherapy in the front-line setting for EGFR-mutated NSCLC patients. At a median follow-up of about 37.8 months, the amivantamab plus lazertinib treatment group demonstrated a hazard ratio of 0.75 compared with osimertinib, with the combination expected to extend median overall survival by at least 12 months versus osimertinib.

The current mainstays of treatment for patients with newly diagnosed, EGFR-mutated, metastatic NSCLC include osimertinib monotherapy, osimertinib plus systemic chemotherapy, and, most recently, amivantamab plus lazertinib. Single-agent osimertinib may be preferred in patients with multiple comorbidities, those who are frail, or older patients, while younger patients with more bulky disease or aggressive disease with high tumor burden may benefit from osimertinib plus systemic chemotherapy or the combination of amivantamab plus lazertinib.

From an equity perspective, coming less often requires less driving for patients and less time out of work, or getting family members to bring patients, making the overall cost of treatment lower. The subcutaneous formulation is also efficient for cancer centers to be able to treat more patients the same day without having patients and nurses being restricted to one chair.