Janssen-Cilag International NV, a subsidiary of Johnson & Johnson, has announced that the Committee for Medicinal Products for Human Use (CHMP) of the Subcutaneous European Medicines Agency (EMA) has issued a positive recommendation for an extension of marketing authorization for the subcutaneous (SC) formulation of Subcutaneous RYBREVANT. This recommendation applies to its use in combination with LAZCLUZE®▼ (lazertinib) for the first-line treatment of adult patients diagnosed with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations.
Additionally, it is recommended as a monotherapy for adult patients with advanced NSCLC who have activating EGFR exon 20 insertion mutations and have experienced disease progression following platinum-based chemotherapy. Subcutaneous For these indications, the suggested administration of SC amivantamab is weekly for the first four weeks (a total of four doses), followed by administration every two weeks starting from Week 5 onward.
Improved Treatment Experience with Subcutaneous Administration
One of the significant benefits of the subcutaneous formulation of amivantamab is its potential to enhance the overall treatment experience for patients. The SC formulation offers a more convenient administration method by significantly reducing the infusion time from hours to just minutes. Additionally, it has demonstrated a marked decrease in the incidence of infusion-related reactions (IRRs) compared to the currently approved intravenous (IV) administration route.
Professor Silvia Novello, M.D., Ph.D., from the Oncology Department at San Luigi Hospital in Orbassano, University of Turin, Italy, emphasized the importance of this advancement. She stated, “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. This positive CHMP opinion represents a significant milestone in the treatment of EGFR-mutated NSCLC, with the potential to bring meaningful benefits to clinical practice. It provides patients with more time to spend with their loved ones and to focus on what matters most to them.”
CHMP Positive Opinion Supported by PALOMA-3 Study Results
The CHMP’s Subcutaneous favorable recommendation is supported by data from the Phase 3 PALOMA-3 study (NCT05388669), which assessed the non-inferiority of the SC formulation in terms of pharmacokinetics (PK), efficacy, and safety in comparison to IV amivantamab. This study evaluated the SC formulation (administered via manual injection) against IV amivantamab, both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC who had experienced disease progression following treatment with osimertinib and platinum-based chemotherapy.
The PALOMA-3 study demonstrated that SC amivantamab was non-inferior to IV amivantamab, successfully 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 seven months, the overall response rate (ORR), which was a secondary endpoint, was recorded at 30 percent (95 percent confidence interval [CI], 24–37) in the SC arm, compared to 33 percent (95 percent CI, 26–39) in the IV arm (relative risk, 0.92; 95 percent CI, 0.70–1.23; P=0.001), confirming the non-inferiority criteria.
Reduced Administration Time and Lower Infusion-Related Reactions
One of the most significant findings from the study was that the administration time for SC amivantamab was dramatically reduced to approximately five minutes, compared to the initial IV infusion time of around five hours (administered across two days). Moreover, the incidence of IRRs was significantly lower, showing a five-fold reduction compared to the IV formulation. These results were highlighted in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and were also published in the Journal of Clinical Oncology.
Dr. Henar Hevia, Ph.D., Senior Director and EMEA Therapeutic Area Lead in Oncology at Johnson & Johnson Innovative Medicine, Subcutaneous reiterated the company’s dedication to improving the patient treatment experience. He stated, “At Johnson & Johnson, we are committed to optimizing every part of the lung cancer treatment journey for patients and healthcare professionals. 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.”
Safety Profile and Lower Risk of Adverse Events
The PALOMA-3 study findings also underscored the safety profile of SC amivantamab. The rate of IRRs among patients treated with SC amivantamab in combination with lazertinib was approximately five times lower than that observed with the IV formulation (13 percent vs. 66 percent, respectively). Furthermore, all reported IRRs in the SC formulation group were mild to moderate (grades 1 and 2), with only one patient experiencing a grade 3 IRR.
Another critical aspect of the study was the use of prophylactic anticoagulation to prevent venous thromboembolism (VTE). Patients who received prophylactic anticoagulation had a lower incidence of VTE (10 percent) compared to those who did not receive anticoagulation (21 percent). Moreover, regardless of anticoagulation status, the VTE incidence was lower in the SC arm compared to the IV arm (9 percent vs. 14 percent, respectively). The occurrence of severe bleeding events (grade 3 to 4) was low, with 2 percent of patients in the SC arm and 0.6 percent in the IV arm experiencing these events. Otherwise, the overall safety profile of SC amivantamab was found to be consistent with that of IV administration.
Among the most common all-grade adverse events occurring in at least 20 percent of patients, paronychia (54 percent in SC vs. 51 percent in IV), hypoalbuminemia (47 percent in SC vs. 37 percent in IV), and rash (46 percent in SC vs. 43 percent in IV) were reported most frequently. These findings reinforce the safety and tolerability of the SC formulation compared to its IV counterpart.
Commitment to Advancing Lung Cancer Treatment
Johnson & Johnson has been at the forefront of innovation in oncology Subcutaneous for over three decades, continuously exploring new approaches to address the unmet needs of patients with cancer. The company remains steadfast in its mission to improve treatment outcomes and provide cutting-edge therapeutic options for patients battling EGFR-mutated NSCLC.
Dr. Joshua Bauml, M.D., Vice President and Lung Cancer Disease Area Stronghold Leader at Johnson & Johnson Innovative Medicine, emphasized the company’s dedication to transforming the treatment landscape for EGFR-mutated NSCLC. He stated, “Building on three decades of oncology innovation, Johnson & Johnson has a deep commitment to exploring innovative approaches to meet the urgent needs of patients. 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.
