The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion recommending the approval of a subcutaneous (SC) formulation of amivantamab for specific non-small cell lung cancer (NSCLC) indications. Janssen-Cilag International NV, a Johnson & Johnson company, announced the recommendation, which includes the use of SC amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations. The CHMP also recommended SC amivantamab as a monotherapy for adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. This decision is poised to enhance treatment convenience and reduce infusion-related reactions for patients.
PALOMA-3 Trial Results
The CHMP's positive opinion is backed by data from the Phase 3 PALOMA-3 study (NCT05388669), which compared the pharmacokinetics, efficacy, and safety of SC amivantamab (administered via manual injection) combined with lazertinib to intravenous (IV) amivantamab and lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and platinum-based chemotherapy. The study met its co-primary endpoints, demonstrating that SC amivantamab was non-inferior to IV amivantamab based on 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 in the SC arm was 30% (95% CI, 24-37) and 33% (95% CI, 26-39) for the IV arm (relative risk, 0.92; 95% CI, 0.70-1.23; P=0.001), meeting the non-inferiority criteria. Notably, the 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). The rate of infusion-related reactions (IRRs) was approximately five-fold lower with the SC formulation (13%) compared to the IV formulation (66%).
Dosing and Administration
The recommended dose regimen for SC amivantamab is 1600 mg (2240 mg for body weight ≥80kg) administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards. When given in combination with lazertinib, SC amivantamab can be administered any time after lazertinib on the same day.
Impact on Patient Care
According to Silvia Novello, M.D., Ph.D., Professor of Medical Oncology at the University of Turin, Italy, the subcutaneous formulation of amivantamab offers an improved treatment experience for patients, significantly reducing administration time and lowering rates of infusion-related reactions compared to the IV therapy. This positive CHMP opinion marks 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.
About Amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody that targets tumors with activating and resistance EGFR mutations and MET mutations and amplifications, while also harnessing the immune system. The European Commission has previously granted marketing authorizations for intravenous amivantamab in several indications, including in combination with lazertinib for first-line treatment of NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as monotherapy for NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. Subcutaneous amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
Non-Small Cell Lung Cancer Landscape
NSCLC accounts for 85% of all lung cancer cases, with EGFR mutations being among the most common driver mutations. These mutations are present in 10-15% of Western patients and 40-50% of Asian patients with NSCLC with adenocarcinoma histology. The five-year survival rate for advanced NSCLC patients with EGFR mutations treated with EGFR TKIs is less than 20%.
