FDA Approves First Subcutaneous Amivantamab Plus Lazertinib for EGFR+ Lung Cancer

The FDA has approved RYBREVANT FASPRO, the first subcutaneous amivantamab, for EGFR-mutated NSCLC, enabling five-minute administration with fewer infusion reactions. In Phase III PALOMA-3, subcutaneous delivery reduced administration-related reactions to 13% versus 66% with IV and improved survival when combined with lazertinib. This approval builds on MARIPOSA data showing an overall survival benefit projected beyond four years.

The U.S. Food and Drug Administration has approved RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), marking a significant advance in the frontline management of EGFR-mutated non small cell lung cancer (NSCLC). The approval introduces the first and only subcutaneous formulation of amivantamab, enabling administration in minutes rather than hours, when used in combination with LAZCLUZE® (lazertinib).

For clinicians and healthcare systems, the shift from intravenous to subcutaneous delivery represents a meaningful reduction in treatment burden. RYBREVANT FASPRO™ shortens administration time from several hours to approximately five minutes, substantially lowering chair time compared with both IV amivantamab and chemotherapy based regimens. The subcutaneous formulation also demonstrated an approximately fivefold reduction in administration related reactions, occurring in 13% of patients compared with 66 percent with IV delivery, alongside lower rates of venous thromboembolism.

Regulatory approval was supported by data from the Phase 3 PALOMA-3 study, which showed pharmacokinetic equivalence between subcutaneous RYBREVANT FASPRO™ and IV amivantamab, meeting both co primary PK endpoints. Beyond PK comparability, updated analyses presented at the 2024 ASCO Annual Meeting and published in the Journal of Clinical Oncology suggested clinically meaningful efficacy advantages for the subcutaneous regimen.

In combination with LAZCLUZE®, the SC arm demonstrated longer duration of response, improved progression free survival, and longer overall survival compared with IV administration. Median overall survival favored the SC regimen with a hazard ratio of 0.62, and at 12 months, 65% of patients receiving SC therapy were alive versus 51% in the IV group.

From a patient perspective, the approval addresses long standing concerns around treatment intensity and quality of life. “Patients now have a simple, chemotherapy-free frontline option that not only targets the disease more precisely but also significantly improves survival,” said Joelle Fathi, D.N.P., Chief Healthcare Delivery Officer, GO2 for Lung Cancer. “With the introduction of RYBREVANT FASPRO, care becomes faster, less invasive, and more aligned with what matters most to patients: time, comfort, and dignity.”

The approval of RYBREVANT FASPRO™ builds on the strong survival foundation established by the RYBREVANT® plus LAZCLUZE® combination in the Phase 3 MARIPOSA trial. In first line patients with EGFR exon 19 deletions or L858R substitution mutations, the combination significantly reduced the risk of death compared with osimertinib, with a hazard ratio of 0.75 at a median follow up of 37.8 months. Median overall survival has not yet been reached, and projections suggest survival exceeding four years, surpassing outcomes historically observed with third generation EGFR TKIs.

According to Dr. Danny Nguyen, principal investigator of PALOMA-3 and MARIPOSA, “The combination of RYBREVANT plus LAZCLUZE changes the biology of the disease by preventing resistance and delivers unmatched overall survival in the first-line setting, while omitting chemotherapy from treatment. Now, with the approval of RYBREVANT FASPRO, we have an entirely new subcutaneous therapy that offers consistent results compared to intravenous delivery, while providing a more patient-centered experience.”

Mechanistically, the regimen addresses a key unmet need in EGFR mutated NSCLC, resistance to third generation TKIs such as osimertinib. By simultaneously targeting EGFR from two angles, inhibiting MET, and engaging the immune system, the combination has shown a reduced emergence of resistance mechanisms. Recent analyses from MARIPOSA presented at the 2025 World Conference on Lung Cancer demonstrated significantly lower rates of MET amplification and secondary EGFR mutations compared with osimertinib.

Safety findings with RYBREVANT FASPRO™ were largely consistent with the known profile of IV amivantamab, with common adverse reactions including rash, nail toxicity, edema, fatigue, gastrointestinal symptoms, and peripheral neuropathy. Importantly, administration related reactions leading to treatment interruption were rare, occurring in only 1 percent of patients receiving the SC regimen with LAZCLUZE®.

Together, the approval of RYBREVANT FASPRO™ and the robust survival data from MARIPOSA position this chemotherapy free, subcutaneous combination as a new benchmark in first line EGFR mutated NSCLC, aligning durable efficacy with a more efficient and patient centered model of care.