Janssen-Cilag International gets European Commission nod for subcutaneous Rybrevant for advanced EGFR-mutated non-small cell lung cancer
Beerse: Janssen-Cilag International NV, a Johnson & Johnson company, has received approval from the European Commission (EC) for an extension of marketing authorisation for a subcutaneous (SC) formulation of RYBREVANT (amivantamab), in combination with LAZCLUZE (lazertinib) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.
For these indications, it is recommended that SC amivantamab is administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards.
This approval follows the recent presentation of final overall survival (OS) results from the Phase 3 MARIPOSA study (NCT04487080), at the 2025 European Lung Cancer Congress (ELCC), showing statistically superior OS with intravenous (IV) amivantamab plus lazertinib versus osimertinib monotherapy in the first-line treatment of patients with advanced EGFR ex19del or L858R substitution mutated NSCLC (hazard ratio [HR], 0.75; 95 percent Confidence Interval [CI], 0.61-0.92; P<0.005).
“While great strides have been made in the treatment of EGFR-mutated non-small cell lung cancer, a critical need still exists for treatment approaches that are not only effective but also more convenient for patients, while optimising experience in the clinic,” said Silvia Novello, M.D., Ph.D., Professor of Medical Oncology in the Oncology Department at San Luigi Hospital in Orbassano, University of Turin, Italy. “The approval of subcutaneous amivantamab will have a meaningful impact on clinical practice, offering patients greater convenience and an improved treatment experience, without compromising on the well-established efficacy of intravenous amivantamab.”
The EC approval is supported by positive results from the Phase 3 PALOMA-3 study (NCT05388669), which evaluated non-inferiority of pharmacokinetics (PK) in addition to efficacy and safety of SC amivantamab (administered via manual injection) compared to IV amivantamab (the already approved route of administration), both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC after disease progression on osimertinib and platinum-based chemotherapy. The study demonstrated that SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary PK endpoints as measured by amivantamab levels in the blood (Ctrough and area under the serum concentration time curve from Cycle 2 day 1 to 15). At a median follow-up of 7 months, the overall response rate (a secondary endpoint) was 30 percent (95 percent confidence interval [CI], 24–37) in the SC arm and 33 percent (95 percent CI, 26–39) for IV (relative risk, 0.92; 95 percent CI, 0.70–1.23; P=0.001), meeting the non-inferiority criteria.
Administration time for SC amivantamab was approximately five minutes, and results showed a five-fold reduction in infusion-related reactions (IRRs) compared to IV administration. These results were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology.
“The approval of subcutaneous amivantamab represents a welcome improvement of the treatment experience for both patients living with EGFR-mutated advanced non-small cell lung cancer and the healthcare professionals who support them,” said Henar Hevia, PhD., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “This advancement presents an important opportunity to reduce the treatment burden, improve quality of life and give patients more time to focus on what truly matters to them.”
The rate of IRRs for patients treated with SC amivantamab combined with lazertinib was shown to be approximately five-fold lower than that observed with the IV formulation (13 percent vs 66 percent, respectively). The majority of IRRs were grades 1 and 2, with one patient experiencing a grade 3 IRR in the SC arm. Preventive blood thinning (prophylactic anticoagulation) was used in most patients in the PALOMA-3 study. Patients receiving prophylactic anticoagulation had lower rates of venous thromboembolic events (VTEs) (10 percent) than those who did not receive prophylaxis (21 percent). Furthermore, VTE incidence was numerically lower in the SC arm vs the IV arm (9 percent vs 14 percent) regardless of anticoagulation status. Severe bleeding risk (grade 3 to 4) was low among patients receiving anticoagulants in both the SC (2 percent) and IV (0.6 percent) arms. Otherwise, the overall safety profile of SC amivantamab is consistent with the known profile of IV administration.
“At Johnson & Johnson, we are dedicated to patient-centered innovation in our mission to address the critical unmet needs in lung cancer treatment and care,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “Our ongoing focus on advancing the clinical development programme for amivantamab reflects our confidence in its potential to become a standard of care for EGFR-and MET-driven lung cancer.”
