U.S. FDA Approves RYBREVANT® FASPRO™ (amivantamab and hyaluronidase-lpuj), Offering the Shortest and Simplest Administration Time for a First-Line Combination Regimen with LAZCLUZE® (lazertinib)
Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) approved RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj), the first and only subcutaneously (SC) administered therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).1 RYBREVANT FASPRO™ is approved across all indications of RYBREVANT® (amivantamab-vmjw).
Compared to intravenous (IV) delivery, RYBREVANT FASPRO™ offers significantly higher patient convenience and lower burden on healthcare resources1-5:
- Reducing administration time from several hours to five minutes (significantly less administration time than chemotherapy-based regimens, which could take up to an hour);
- Demonstrating an approximately fivefold reduction in administration-related reactions (ARRs) (13 percent in SC vs 66 percent in IV arm); and
- Reducing venous thromboembolism (VTE) incidence (11 percent in SC vs 18 percent in IV arm).
Based on the results from the Phase 3 PALOMA-3 study (NCT05388669), RYBREVANT FASPRO™ delivered consistent results to RYBREVANT®, meeting both co-primary pharmacokinetic (PK) endpoints as measured by amivantamab levels in the blood [Ctrough on Cycle (C) 2 Day (D) 1 or C4D1 and C2 area under the curve (AUCD1-D15)].1,7 Results from PALOMA-3 were first presented as a late-breaking oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.
Data presented at ASCO in 2024 and published in the Journal of Clinical Oncology also found that the SC arm showed longer duration of response (DoR), improved progression-free survival (PFS), and longer overall survival (OS) compared to the IV arm. Median OS was notably higher for patients treated with the SC arm in combination with LAZCLUZE® (HR 0.62; 95 percent CI, 0.42–0.92; nominal P=0.02). At 12 months, 65 percent of patients receiving SC were alive, compared with 51 percent treated with IV.7
“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. 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.”
This milestone builds upon the statistically significant and clinically meaningful OS data demonstrated with RYBREVANT® plus LAZCLUZE® for patients with untreated (first-line) locally advanced or metastatic NSCLC with EGFR exon 19 deletions (ex19del) or L858R substitution mutations in the Phase 3 MARIPOSA study.
At a median follow-up of 37.8 months, RYBREVANT® plus LAZCLUZE® showed a statistically significant reduction in the risk of death compared to osimertinib (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.61-0.92, P=0.0048). Median OS was not yet reached with the combination (95 percent CI, 42.9-not estimable) and the OS benefit is projected to exceed four years, which is at least one year beyond the median of three years observed with osimertinib (36.7 months; 95 percent CI, 33.4-41.0).6
“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 Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology & Therapeutics Research, 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.”
“The approval of RYBREVANT FASPRO is a pivotal step forward, as EGFR+ NSCLC patients have previously faced limited treatment options,” explains Biljana Naumovic, President, Solid Tumor, Johnson & Johnson Innovative Medicine. “Now, patients are gaining greater access to this transformative treatment, as well as the tools needed to proactively manage common dermatological effects.”
Lower rates of ARRs (13 percent vs. 66 percent) were observed with RYBREVANT FASPRO™ compared to IV administration. The incidence of ARRs leading to interruption of any study treatment was also substantially lower in the RYBREVANT FASPRO™ and LAZCLUZE® arm (1.0 percent). When treated with RYBREVANT FASPRO™ plus LAZCLUZE® and prophylactic anticoagulant use (n=164), a VTE rate of 7 percent was observed, representing a return to baseline risk for patients with advanced NSCLC.
Rates of VTE were lower (11 percent vs. 18 percent) in all patients treated with RYBREVANT FASPRO™ plus with LAZCLUZE®, compared to patients treated with IV administration.1 Overall, the safety profile of RYBREVANT FASPRO™ was largely consistent with the known profile of IV administration, and in combination with LAZCLUZE®. The most common adverse reactions of RYBREVANT FASPRO™ in combination with LAZCLUZE® (≥ 20 percent) were rash, nail toxicity, musculoskeletal pain, edema, fatigue, nausea, hemorrhage,peripheral neuropathy, decreased appetite, constipation, diarrhea, pruritus, and dry skin.1
Access to RYBREVANT FASPRO™
Johnson & Johnson offers comprehensive access and support information and resources to assist patients in gaining access to RYBREVANT FASPRO™. Our patient support program, withMe‡, is available to provide personalized support to help patients start and stay on their Johnson & Johnson medicines. RYBREVANT withMe helps providers support their patients by verifying patients’ insurance coverage, providing information on Prior Authorization and Appeals processes and educating on reimbursement processes. Patients can connect to RYBREVANT withMe to receive cost support, regardless of insurance type, free, personalized one-on-one support from a Care Navigator, and resources and community connections. Learn more at RYBREVANTwithMe.com or by calling 833-JNJ-wMe1 (833-565-9631).
About the PALOMA-3 Study
PALOMA-3 (NCT05388669), which enrolled 418 patients, is a randomized, open-label Phase 3 study evaluating the PK, efficacy and safety of RYBREVANT FASPRO™ (administered via manual injection) plus LAZCLUZE® compared to RYBREVANT®-based regimens and LAZCLUZE® in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. The co-primary PK endpoints of the study were trough concentration [Ctrough on Cycle (C) 2 Day (D) 1 or C4D1 and C2 area under the curve (AUCD1-D15)]. Key secondary endpoints were ORR and PFS. OS was a predefined exploratory endpoint. Prophylactic anticoagulation was recommended for the first four months of treatment.8
About the MARIPOSA Study
MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT® plus LAZCLUZE® versus osimertinib and versus LAZCLUZE® alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints include OS, ORR, DoR, progression-free survival after first subsequent therapy (PFS2) and intracranial PFS.9
Resistance to third-generation TKIs, such as osimertinib (when given alone or with chemotherapy), remains a major barrier to long-term disease control.10 The combination regimen RYBREVANT® plus LAZCLUZE® uses a triple mode of action: targeting EGFR mutations from two angles, blocking MET, and engaging the immune system.6 This approach has the potential to change the natural history of the disease by reducing the spectrum and complexity of acquired resistance mechanisms.12
A new analysis from MARIPOSA, presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Congress on Lung Cancer (WCLC), demonstrated that the combination significantly reduced the development of EGFR– and MET-driven resistance compared with osimertinib in the first-line setting. MET amplifications occurred in three percent of patients on the combination vs 13 percent on osimertinib (P=0.002), and secondary EGFR mutations (such as C797S) were significantly lower for RYBREVANT® plus LAZCLUZE® (1 percent vs 8 percent; P=0.01). Notably, acquired MET amplification led to early discontinuation in 23 percent of patients on osimertinib within six months, compared with four percent on RYBREVANT® plus LAZCLUZE®.10,11
About RYBREVANT®
RYBREVANT® (amivantamab-vmjw) is a first-in-class, fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity.
Data across multiple Phase 3 studies, including MARIPOSA and PALOMA-3, have demonstrated the clinical benefit of RYBREVANT® -based regimens in improving PFS and OS in advanced EGFR-mutated NSCLC.
RYBREVANT® is approved in the U.S. across four indications in EGFR-mutated NSCLC, including two in the first-line setting and two in the second-line, or patients with either exon 19 deletions, exon 21 L858R mutations, or exon 20 insertion mutations, as monotherapy or in combination with lazertinib or chemotherapy.
The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)§[1] include amivantamab-vmjw (RYBREVANT®) across multiple treatment settings, including its recent inclusion as a NCCN Category 1 preferred option when used with lazertinib (LAZCLUZE®) for first-line treatment of people with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations; see the latest NCCN Guidelines® for NSCLC for complete information.‖¶
The NCCN Guidelines for Central Nervous System Cancers also identify amivantamab-vmjw (RYBREVANT®)-based regimens, including the combination with lazertinib (LAZCLUZE®), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases.‖¶
RYBREVANT FASPRO™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
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