PALOMA-2: Subcutaneous Amivantamab with Lazertinib Shows Efficacy and Safety in EGFR-Mutated NSCLC

Johnson & Johnson recently unveiled promising data from the Phase 2 PALOMA-2 study at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The study evaluates the efficacy and safety of subcutaneous (SC) amivantamab in combination with lazertinib as a first-line treatment for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR exon 19 deletions (ex19del) or L858R mutations. The data indicate that SC amivantamab results in comparable response rates to the intravenous (IV) formulation, with significantly lower rates of infusion-related reactions (IRRs) and shorter treatment times.

The PALOMA-2 study focuses on patients with treatment-naive, EGFR ex19del, or L858R-mutated advanced NSCLC. The study comprises two cohorts: Cohort 1, where prophylactic anticoagulation is recommended, and Cohort 6, where it is mandatory. As of January 6, 2024, the study had enrolled 68 patients in Cohort 1 and 58 in Cohort 6. At a median follow-up of 8.6 months, SC amivantamab combined with lazertinib demonstrated an overall response rate (ORR) of 77% as assessed by investigators and 79% by blinded independent central review. This response rate is similar to the 86% ORR observed with IV amivantamab in combination with lazertinib in the Phase 3 MARIPOSA study.

An advantage of the SC formulation is the notably reduced IRR rates, with SC administration associated with only 15% IRRs compared to higher rates observed with the IV formulation. Additionally, the SC administration time averages around five minutes, significantly shorter than the 2-4 hours required for IV administration. Overall, the safety profile for SC amivantamab remains consistent with previous reports, showing no new safety issues. Common adverse events included paronychia (71%), rash (61%), and hypoalbuminemia (48%).

Discontinuation of treatment due to adverse events was relatively low, occurring in about 9% of patients. Venous thromboembolic events (VTEs) were reported in 18% of patients in Cohort 1 and 7% in Cohort 6, with prophylactic anticoagulation proving effective in reducing the incidence of VTEs.

Kiran Patel, M.D., Vice President of Clinical Development for Solid Tumors at Johnson & Johnson Innovative Medicine, highlighted the safety and tolerability of SC amivantamab, indicating its potential as an important first-line therapy for patients with EGFR-mutant lung cancer. The findings may address the current unmet need for more tolerable and effective treatments in this patient population.

About RYBREVANT®

RYBREVANT® (amivantamab-vmjw) is a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity. Approved in the U.S., Europe, and other markets, it treats adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations. In its SC formulation, amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) for enhanced drug delivery.

Recent regulatory submissions by Johnson & Johnson include a supplemental Biologics License Application (sBLA) to the U.S. FDA and a New Drug Application (NDA) for RYBREVANT® in combination with lazertinib for first-line treatment of EGFR-mutated NSCLC. This submission is based on the Phase 3 MARIPOSA study and has been granted Priority Review. Additionally, a marketing authorization application was submitted to the European Medicines Agency (EMA) for the same combination.

RYBREVANT® continues to be evaluated in numerous clinical trials, such as the Phase 1 PALOMA study, Phase 2 PALOMA-2 study, and Phase 3 PALOMA-3 study, among others. These studies aim to further assess its efficacy and safety across various patient populations with advanced or metastatic NSCLC.

Globally, lung cancer remains one of the most common cancers, with NSCLC accounting for 80-85% of all cases. Among NSCLC, EGFR mutations are significant drivers, particularly in Western and Asian populations. These studies and ongoing research emphasize the commitment to finding effective and tolerable treatments for patients with EGFR-mutated NSCLC.