Amivantamab Biologics License Application submitted to FDA for EGFR-mutated lung cancer

Johnson & Johnson has announced the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for a fixed combination of amivantamab and recombinant human hyaluronidase for subcutaneous administration (SC amivantamab). This application is based on the promising results from the Phase 3 PALOMA-3 study, which showed a significant reduction in infusion-related reactions and shorter administration time when compared to the intravenous (IV) administration of RYBREVANT® (amivantamab-vmjw) in non-small cell lung cancer (NSCLC) patients.

The PALOMA-3 study, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology, revealed that SC amivantamab not only reduced infusion reactions by five-fold but also demonstrated longer overall survival, progression-free survival, and duration of response in patients with NSCLC harboring EGFR exon 19 deletion or L858R mutations. These results were unprecedented in studies comparing IV and SC administration.

Johnson & Johnson's BLA submission includes data from the Phase 2 PALOMA-2 study, which evaluated SC amivantamab in various settings where IV amivantamab had been previously submitted for approval. This submission aims to support dosing schedules of every two and three weeks. Dr. Kiran Patel, Vice President of Clinical Development for Solid Tumors at Johnson & Johnson Innovative Medicine, emphasized the clinical significance of this new subcutaneous option, highlighting its potential to improve the treatment experience for patients, oncologists, and nursing staff.

This submission follows recent milestones for the IV formulation of RYBREVANT®, including its FDA approval in combination with chemotherapy for first-line treatment of NSCLC patients with EGFR exon 20 insertion mutations and a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for the same indication in Europe.

The PALOMA-3 study enrolled 418 patients and is a randomized, open-label Phase 3 trial assessing the pharmacokinetics, efficacy, and safety of SC amivantamab combined with lazertinib versus IV amivantamab combined with lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC. Key secondary endpoints included objective response rate and progression-free survival, with overall survival as a predefined exploratory endpoint.

Additionally, the PALOMA-2 study, an open-label Phase 2 trial, evaluated SC amivantamab combined with lazertinib and/or chemotherapy in first-line treatment settings for patients with EGFR-mutated advanced or metastatic NSCLC. The study enrolled a total of 126 patients across two cohorts, with the primary endpoint being the objective response rate as assessed by the investigator.

RYBREVANT® (amivantamab-vmjw) is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. It is approved in the U.S., Europe, and other markets for treating adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. The subcutaneous formulation of amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), utilizing Halozyme's ENHANZE® drug delivery technology.

Overall, Johnson & Johnson is advancing the treatment landscape for NSCLC with the development and regulatory submission of SC amivantamab. The new subcutaneous administration method offers a significant improvement in convenience and safety, potentially transforming the treatment experience for both patients and healthcare providers. The company is committed to working with global regulators to gain approval for this innovative therapy.