PALOMA-3 study: Five-minute subcutaneous amivantamab cuts infusion reactions fivefold

Johnson & Johnson has revealed groundbreaking data from the Phase 3 PALOMA-3 study, which evaluated the efficacy of subcutaneous (SC) amivantamab combined with lazertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) showing EGFR exon 19 deletion (ex19del) or L858R mutations. The study results highlighted that SC amivantamab, with its shorter administration time and reduced infusion-related reactions (IRRs), is non-inferior to the currently approved intravenous (IV) formulation of RYBREVANT® (amivantamab-vmjw).

Key findings from the study were disclosed at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and were featured in the Best of ASCO 2024, emphasizing Johnson & Johnson's leadership in oncology research. The PALOMA-3 study showed that SC amivantamab combined with lazertinib had comparable pharmacokinetics and efficacy to the IV formulation. Notably, the subcutaneous administration reduced infusion time from five hours over two days to just five minutes and decreased IRRs by fivefold.

Dr. Natasha B. Leighl, a medical oncologist at the Princess Margaret Cancer Centre in Toronto, presented the data, highlighting the potential improvement in patient treatment experience. The study demonstrated that at a median follow-up of seven months, the overall response rate (ORR) was 30% for the SC arm and 33% for the IV arm, meeting the non-inferiority criteria. Additionally, SC amivantamab showed longer duration of response (DoR), progression-free survival (PFS), and overall survival (OS). Median DoR was 11.2 months for SC compared to 8.3 months for IV, and PFS was 6.1 months versus 4.3 months, respectively. Furthermore, patients receiving SC treatment had significantly longer OS, with 65% alive at 12 months compared to 51% in the IV group.

The SC formulation's efficacy is potentially enhanced by its absorption via the lymphatic system, possibly boosting immune-mediated activity. The safety profile of SC amivantamab was consistent with the IV administration. Common adverse events included paronychia, hypoalbuminemia, and rash, with no grade 4 or 5 IRRs reported. The incidence of IRRs was significantly lower in the SC group at 13% compared to 66% in the IV group.

Prophylactic anticoagulation was used safely and effectively in most patients, reducing venous thromboembolic events (VTE). The VTE incidence was lower in the SC arm at 9% compared to 14% in the IV arm. Severe bleeding risks were minimal and comparable between the SC and IV arms.

Johnson & Johnson has submitted a marketing application to the European Medicines Agency (EMA) for the approval of SC amivantamab combined with lazertinib for first-line treatment of locally advanced or metastatic NSCLC with EGFR ex19del or L858R mutations. The company plans to pursue regulatory submissions for SC amivantamab in other markets, including the United States.

RYBREVANT® (amivantamab-vmjw) is a bispecific antibody targeting EGFR and MET, approved for treating adult patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. The SC formulation includes recombinant human hyaluronidase PH20, enhancing drug delivery.

The PALOMA-3 study, enrolling 418 patients, evaluated the pharmacokinetics, efficacy, and safety of SC amivantamab combined with lazertinib compared to IV administration in advanced or metastatic NSCLC after progression on osimertinib and chemotherapy. The study's co-primary endpoints were trough concentration and area under the curve, with secondary endpoints including ORR and PFS.

Johnson & Johnson is dedicated to advancing the treatment of EGFR-mutated NSCLC through innovative approaches and looks forward to transforming first-line treatment options. The company continues to explore the potential of RYBREVANT® in various clinical trials, aiming to improve outcomes for patients with NSCLC.