Johnson & Johnson has filed a Biologics License Application (BLA) with the U.S. Food and Drug Administration (FDA) for a fixed combination of amivantamab and recombinant human hyaluronidase intended for subcutaneous administration. This application covers all currently approved or proposed indications for intravenous RYBREVANT® (amivantamab-vmjw) in certain patients with non-small cell lung cancer (NSCLC).

The Phase 3 PALOMA-3 study's results, presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology, showed that subcutaneous amivantamab offers comparable overall response rates to its intravenous counterpart in patients with NSCLC who have EGFR exon 19 deletions or L858R mutations. This formulation also demonstrated significantly reduced administration times, a fivefold decrease in infusion-related reactions, and improvements in overall survival, progression-free survival, and duration of response. These findings represent significant advancements in the treatment options available for these patients. The BLA submission also includes data from the Phase 2 PALOMA-2 study, which investigates subcutaneous amivantamab in settings previously approved for intravenous administration, and proposes dosing schedules every two and three weeks.

Johnson & Johnson Innovative Medicine, noted that "RYBREVANT administered intravenously has been a cornerstone treatment for patients with EGFR-mutated NSCLC. The introduction of this subcutaneous option, which can be administered in about five minutes, represents a significant step forward that could enhance the treatment experience for patients, oncologists, and nursing staff. We are eager to collaborate with the FDA and global regulatory authorities throughout the review process."

This submission follows important milestones for the RYBREVANT® intravenous formulation, including its approval in combination with chemotherapy as the first FDA-approved treatment for the first-line therapy of patients with NSCLC who have EGFR exon 20 insertion mutations, based on the Phase 3 PAPILLON study, and a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) for this indication in Europe.

The Phase 3 PALOMA-3 study (NCT05388669) included 418 patients and is a randomized, open-label trial assessing the pharmacokinetics, efficacy, and safety of subcutaneous amivantamab administered via manual injection, combined with lazertinib compared to intravenous amivantamab and lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. Primary pharmacokinetic endpoints included trough concentration and area under the curve, with secondary endpoints focusing on objective response rate and progression-free survival, while overall survival was a predefined exploratory endpoint.

The Phase 2 PALOMA-2 study (NCT05498428) is examining the efficacy, safety, and pharmacokinetics of first-line subcutaneous amivantamab administered via manual injection, combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC.

RYBREVANT® (amivantamab-vmjw) is a fully human bispecific antibody that targets EGFR and MET with immune cell-directed activity, approved in the U.S., Europe, and other markets worldwide for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy. This subcutaneous formulation is co-formulated with recombinant human hyaluronidase PH20, utilizing Halozyme's ENHANZE® drug delivery technology.

RYBREVANT® is also approved in the U.S. in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. Recent applications to the European Medicines Agency (EMA) seek approval for this combination treatment.

The BLA also includes submissions related to the combination of RYBREVANT® and lazertinib for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, based on the Phase 3 MARIPOSA study, which has received Priority Review from the FDA.

The NCCN Clinical Practice Guidelines in Oncology for NSCLC recommend next-generation sequencing-based strategies for detecting EGFR exon 20 insertion variants and include RYBREVANT® in various treatment contexts based on EGFR mutation status.

RYBREVANT® is currently under investigation in multiple clinical trials for NSCLC, evaluating various formulations and combinations with other therapies to enhance treatment outcomes.

Lazertinib, an oral third-generation EGFR tyrosine kinase inhibitor, targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR, and is being studied in collaboration with Yuhan Corporation.

NSCLC, which accounts for 80 to 85% of all lung cancer cases, is characterized by mutations such as EGFR alterations, which are common in both Western and Asian populations. EGFR exon 20 insertion mutations, while less common, are significant due to their association with distinct treatment responses.

RYBREVANT® carries several warnings and precautions, including risks of infusion-related reactions, interstitial lung disease/pneumonitis, dermatologic adverse reactions, ocular toxicity, and embryo-fetal toxicity. Detailed safety profiles are provided based on clinical trial data.

 

Source: prnewswire.com

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