Janssen’s subcutaneous amivantamab gains CHMP backing for EGFR-mutated lung cancer

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the extension of marketing authorisation for subcutaneous amivantamab treatment. This formulation of RYBREVANT (amivantamab), developed by Janssen-Cilag International NV, a Johnson & Johnson company, represents a significant step forward in the treatment of advanced non-small cell lung cancer (NSCLC), particularly in patients with epidermal growth factor receptor (EGFR) mutations.

The recommendation applies to both combination therapy and monotherapy approaches. In combination with LAZCLUZE (lazertinib), subcutaneous amivantamab treatment is recommended as a first-line therapy for adult patients with EGFR-mutated lung cancer, specifically those with exon 19 deletions or exon 21 L858R substitution mutations. Additionally, it is approved as a standalone treatment for patients with activating EGFR exon 20 insertion mutations who have progressed following platinum-based chemotherapy. The treatment regimen involves weekly doses during the first month, followed by bi-weekly administrations from the fifth week onward.

Why is the CHMP’s recommendation for subcutaneous amivantamab treatment significant?

The positive CHMP opinion is based on compelling data from the Phase 3 PALOMA-3 study, which demonstrated that subcutaneous amivantamab treatment is non-inferior to the traditional intravenous (IV) formulation in terms of pharmacokinetics, meeting both co-primary endpoints related to drug concentration and exposure. The subcutaneous version also offers several clinical advantages, including a five-fold reduction in infusion-related reactions (IRRs) and a lower incidence of venous thromboembolic events (VTEs), key concerns in cancer treatment.

One of the most notable benefits is the significant reduction in administration time. While IV infusions can take several hours, the subcutaneous formulation can be administered in approximately five minutes. This improvement not only enhances patient comfort but also reduces the burden on healthcare systems.

Professor Silvia Novello, an oncology expert from the University of Turin, Italy, highlighted the impact of this advancement, stating that subcutaneous amivantamab treatment “improves the overall patient experience, allowing them to spend more time with their loved ones rather than undergoing lengthy hospital procedures.”

How does subcutaneous amivantamab compare to intravenous therapy?

The PALOMA-3 trial enrolled 418 patients with EGFR-mutated lung cancer to compare the pharmacokinetics, efficacy, and safety of subcutaneous amivantamab treatment with its IV counterpart. The study’s findings were groundbreaking: the objective response rate was 30% in the subcutaneous group and 33% in the IV group, meeting the criteria for non-inferiority.

Importantly, the incidence of IRRs was significantly lower in the subcutaneous arm, with only 13% of patients experiencing reactions compared to 66% in the IV arm. Most IRRs were mild to moderate, with just one severe case reported in the subcutaneous group. In addition, the rate of VTEs was reduced in the subcutaneous group (9%) compared to the IV group (14%), demonstrating improved safety outcomes.

These results were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and later published in the Journal of Clinical Oncology, further validating the clinical benefits of subcutaneous amivantamab treatment.

What are the expert opinions on subcutaneous amivantamab’s impact?

Experts in oncology are optimistic about the future of subcutaneous amivantamab treatment. Dr Henar Hevia, Senior Director at Johnson & Johnson Innovative Medicine, emphasised that the CHMP’s recommendation marks a pivotal moment in lung cancer treatment. “This is more than just a regulatory milestone; it’s a leap forward in providing patients with effective, safe, and convenient care,” she said.

Dr Joshua Bauml, Vice President of Lung Cancer Disease Area Stronghold at Johnson & Johnson, highlighted the company’s long-standing commitment to oncology innovation. He noted that the approval of subcutaneous amivantamab treatment aligns with Johnson & Johnson’s mission to improve outcomes for patients with advanced non-small cell lung cancer, particularly those affected by EGFR mutations.

What does the future hold for EGFR-mutated lung cancer treatments?

The CHMP’s positive opinion is expected to pave the way for broader adoption of subcutaneous amivantamab treatment across Europe, pending final approval from the European Commission. This could significantly improve the standard of care for patients with EGFR-mutated lung cancer, offering a treatment that is not only effective but also more convenient and safer than traditional IV therapy.

Additionally, the combination of amivantamab with lazertinib, an EGFR tyrosine kinase inhibitor (TKI) developed in collaboration with Yuhan Corporation, has shown promising results. Lazertinib targets both the T790M mutation and activating EGFR mutations, providing a comprehensive approach to managing advanced non-small cell lung cancer.

As the landscape of lung cancer treatment continues to evolve, the introduction of subcutaneous amivantamab treatment represents a major step forward, reflecting the ongoing commitment of researchers, clinicians, and pharmaceutical companies to improving patient outcomes and quality of life.