Rybrevant Faspro FDA-Approved as First Sub-Q Therapy for EGFR NSCLC

The U.S. Food and Drug Administration (FDA) have granted approval to Rybrevant Faspro (amivantamab and hyaluronidase-lpuj), the first and only subcutaneous therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) across all indications, according to a news release from Johnson & Johnson.

Importantly, subcutaneous treatment allows for the administration of the medication into the skin through a small needle, ultimately reducing administration time from hours to minutes and significantly reducing administration-related reactions compared with intravenous (IV) delivery and other chemotherapy-based regimens. Overall, this form of administration can be significantly more convenient for the patient and is a lower burden on healthcare resources, the release added.

“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, chief healthcare delivery officer for 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. This therapy reduces the physical and emotional burden of lengthy infusions, giving patients and their families the opportunity to reclaim precious moments and focus on living, rather than treatment.”

Understanding the Context of the Rybrevant Faspro FDA Approval

Data from the phase 3 PALOMA-3 study supported the regulatory decision. The PALOMA-3 study included 418 patients and compared treatment with Lazcluze (lazertinib) with either Rybrevant Faspro (given subcutaneously) or intravenous Rybrevant (amivantamab-vmjw) in people with EGFR-mutated advanced or metastatic NSCLC who had already received prior therapy.

The study aimed to better understand how the body absorbs and processes the drug (pharmacokinetics) as its main goal. Researchers also assessed tumor response and progression-free survival, as well as overall survival as an additional goal

Rybrevant Faspro met both co-primary pharmacokinetic end points of the clinical trial, as measured by quantifying concentration levels of Rybrevant in the blood. Findings from PALOMA-3 were initially presented as a late-breaking oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and subsequently published in the Journal of Clinical Oncology.

Data also showed that patients receiving the subcutaneous formulation experienced longer duration of response, improved progression-free survival, and longer overall survival compared with the IV formulation. Notably, the median overall survival was higher for patients treated with the subcutaneous treatment at 12 months: 65% of patients receiving subcutaneous therapy were alive compared with 51% treated with IV treatment.

According to the news release, the FDA approval builds on the statistically significant and clinically meaningful overall survival benefit observed in the phase 3 MARIPOSA study, designed to evaluate Rybrevant plus Lazcluze among patients with untreated, locally advanced or metastatic NSCLC harboring EGFR exon 19 deletions (ex19del) or L858R substitution mutations.

“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,” said Dr. Danny Nguyen, assistant clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope, and principal investigator for the PALOMA-3 and MARIPOSA studies. “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.”

Fewer Infusion Reactions and Lower Blood Clot Risk Make Rybrevant Faspro Safer for Patients

Rybrevant Faspro was associated with fewer infusion-related reactions than the IV regimen, occurring in 13% of patients versus 66%, respectively. Additionally, only 1% of patients needed to stop treatment due to these reactions when taking Rybrevant Faspro with Lazcluze.

For patients receiving preventive blood-thinning medication, the risk of blood clots (venous thromboembolism; VTE) was 7%, returning to typical levels seen in advanced NSCLC. Overall, VTE rates were lower with the subcutaneous therapy compared to IV treatment (11% vs 18%, respectively).

The overall safety profile of Rybrevant Faspro was similar to IV administration, whether used alone or with Lazcluze. The most common side effects (occurring in at least 1 in 5 patients) included rash, nail changes, muscle or joint pain, swelling, fatigue, nausea, bleeding, nerve changes, decreased appetite, constipation, diarrhea, itching, and dry skin.

“The approval of Rybrevant Faspro is a pivotal step forward, as EGFR-positive NSCLC patients have previously faced limited treatment options,” Biljana Naumovic, president of Solid Tumor at Johnson & Johnson Innovative Medicine, concluded in the news release. “Now, patients are gaining greater access to this transformative treatment, as well as the tools needed to proactively manage common dermatological effects.”

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),” by Johnson & Johnson. News release; Dec. 17, 2025.
2. “FDA to Review Subcutaneous Rybrevant for NSCLC Treatment,” by Alex Biese. CURE: June 24, 2024. https://www.curetoday.com/view/fda-to-review-subcutaneous-rybrevant-for-nsclc-treatment
3. “Rybrevant Plus Leclaza May Be New Standard for EGFR-Mutant Lung Cancer,” by Brielle Benyon. CURE; June 1, 2024. https://www.curetoday.com/view/rybrevant-plus-leclaza-may-be-new-standard-for-egfr-mutant-lung-cancer

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