CHMP recommends subcutaneous RYBREVANT®▼ (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer
Data from the Phase 3 PALOMA-3 study showed non-inferiority to intravenous administration meeting both co-primary pharmacokinetic (PK) endpoints, as well as a five-fold reduction in infusion-related reactions and fewer venous thromboembolic events1
CHMP has issued a positive opinion for an extension of marketing authorisation for subcutaneous amivantamab dosed every two weeks
BEERSE, BELGIUM, Feb. 03, 2025 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has recommended 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 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.1
“The subcutaneous formulation of amivantamab offers an improved treatment experience for patients, reducing administration time from hours to minutes and substantially lowering rates of infusion-related reactions compared to the currently approved intravenous therapy,” 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.* “This positive CHMP opinion is a welcome milestone in the treatment of EGFR-mutated NSCLC, with the ability to make a meaningful difference in clinical practice and provide patients with more time to spend with their loved ones and to focus on what matters most to them.”
The CHMP positive opinion 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 intravenous (IV) amivantamab (the currently approved route of administration), both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and platinum-based chemotherapy.1,2 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).1 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.1
Administration time for SC amivantamab was reduced to approximately five minutes compared to around five hours for the first IV amivantamab infusion (across two days) and showed a five-fold reduction in infusion-related reactions (IRRs).1 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.1,3
“At Johnson & Johnson, we are committed to optimising every part of the lung cancer treatment journey for patients and healthcare professionals,” said Henar Hevia, PhD., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The positive CHMP recommendation for subcutaneous amivantamab takes us one step closer to making this a reality, providing the established efficacy benefits of IV amivantamab with improved safety outcomes and greater convenience for patients.”
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).1 All IRRs were grades 1 and 2, with one patient experiencing a grade 3 IRR in SC arm.1 Preventive blood thinning (prophylactic anticoagulation) was used in most patients in the PALOMA-3 study.1 Patients receiving prophylactic anticoagulation had lower rates of VTE (10 percent) than those without prophylaxis (21 percent).1 Furthermore, VTE incidence was numerically lower in the SC arm vs the IV arm (9 percent vs 14 percent) regardless of anticoagulation status.1 Severe bleeding risk (grade 3 to 4) was low among patients receiving anticoagulants in the SC (2 percent) and IV (0.6 percent) arms.1 Otherwise, the overall safety profile of SC amivantamab is consistent with the known profile of IV administration.1 Of the all-grade adverse events that occurred in ≥20 percent of patients, for SC amivantamab compared to IV, the most common were paronychia (54 percent vs 51 percent), hypoalbuminemia (47 percent vs 37 percent) and rash (46 percent vs 43 percent), respectively.1
“Building on three decades of oncology innovation, Johnson & Johnson has a deep commitment to exploring innovative approaches to meet the urgent needs of patients," said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. "We look forward to bringing this new treatment option to patients in Europe, as we advance our ambition to transform outcomes in EGFR-mutated NSCLC.”
