FDA Approval of Subcutaneous Amivantamab: Transforming Lung Cancer Care

Johnson & Johnson has announced FDA approval for RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), marking the first and only subcutaneously administered treatment for patients with EGFR-mutated non-small cell lung cancer (NSCLC). This new formulation of RYBREVANT® significantly reduces treatment burden while delivering outcomes comparable to its intravenous (IV) counterpart.

Developed for patients with EGFR exon 19 deletions or L858R substitution mutations, RYBREVANT FASPRO™ is approved across all the same indications as IV-administered RYBREVANT®, including in combination with LAZCLUZE® (lazertinib) and with chemotherapy. The subcutaneous (SC) route brings measurable improvements in convenience, safety, and quality of life.

Clinical findings from the Phase 3 PALOMA-3 study demonstrated that RYBREVANT FASPRO™ matched IV RYBREVANT® in pharmacokinetics and therapeutic impact while offering significant advantages in administration and tolerability. The SC formulation reduced administration time to five minutes, compared to several hours for IV infusions. It also lowered the rate of administration-related reactions from 66% in the IV group to 13% in the SC group, and showed a decrease in venous thromboembolism (VTE) incidence (11% vs. 18%).

Importantly, efficacy outcomes favored the SC arm: longer duration of response, progression-free survival, and overall survival were observed compared to IV delivery. At the 12-month mark, 65% of patients receiving SC administration were alive, compared to 51% in the IV arm. These data were initially presented at the 2024 ASCO Annual Meeting and published in the Journal of Clinical Oncology.

The approval of RYBREVANT FASPRO™ builds on momentum from the MARIPOSA study, which demonstrated that the RYBREVANT® and LAZCLUZE® combination significantly extended survival beyond the three-year median seen with osimertinib. The combination’s triple mechanism—targeting EGFR from two angles, blocking MET, and engaging immune pathways—also showed reduced development of treatment resistance, including fewer MET amplifications and secondary EGFR mutations.

Safety findings were consistent with IV RYBREVANT®. The most common adverse events with SC administration included rash, nail toxicity, musculoskeletal pain, and edema. However, the lower rates of administration-related and infusion-related complications, as well as reduced VTE risks—particularly when combined with prophylactic anticoagulation—suggest the SC route may offer a better tolerability profile for many patients.

Patients also benefit from RYBREVANT withMe, a support program offering insurance navigation, financial assistance, and one-on-one care navigation services. This program aims to streamline access and adherence across all payer types.

The approval of RYBREVANT FASPRO™ marks a pivotal moment in NSCLC care—offering a chemotherapy-free, precision-targeted therapy that simplifies treatment logistics and prioritizes patient comfort.

As EGFR-mutated NSCLC continues to present challenges with resistance and limited long-term survival, this innovation offers a more accessible and humane treatment paradigm.