New formulation showed non-inferiority to intravenous administration in fourth positive Phase 3 study in RYBREVANT® clinical program
Longer overall survival, progression-free survival and duration of response shown with subcutaneous amivantamab; featured in Best of ASCO 2024
RYBREVANT® marketing application submitted to European Medicines Agency based on PALOMA-3 study
CHICAGO, May 31, 2024 /PRNewswire/ — Johnson & Johnson announced today first data from the Phase 3 PALOMA-3 study evaluating subcutaneous (SC) amivantamab combined with lazertinib in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletion (ex19del) or L858R mutations. Study results showed non-inferior efficacy and pharmacokinetics for SC amivantamab combined with lazertinib compared to intravenous (IV) administration, the currently approved formulation of RYBREVANT® (amivantamab-vmjw). Administration time for SC amivantamab was reduced to approximately five minutes from five hours (across two days) and showed a five-fold reduction in infusion-related reactions (IRRs). These late-breaking results, which are the Company’s fourth positive Phase 3 readout for the RYBREVANT® clinical program, were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #LBA8505).1 Data were also selected for the Best of ASCO 2024 Meetings, highlighting the cutting-edge science and leading research in oncology from Johnson & Johnson.
“The PALOMA-3 data show that subcutaneous amivantamab offers shorter infusion times and lower rates of infusion-related reactions and venous thromboembolism with pharmacokinetics and efficacy comparable to the current IV administration,” said Dr. Natasha B. Leighl*, medical oncologist at the Princess Margaret Cancer Centre in Toronto, Canada, and the presenting author. “I look forward to seeing how these findings can make a meaningful difference in clinical practice by potentially improving the treatment experience for patients with EGFR-mutated non-small cell lung cancer.”
Results showed SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary pharmacokinetic (PK) efficacy endpoints as measured by amivantamab levels in the blood (Ctrough and area under the serum concentration time curve from day 1 to 15).1
At a median follow-up of seven months, the overall response rate was 30 percent (95 percent confidence interval [CI], 24–37) in the subcutaneous 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 noninferiority criteria. SC amivantamab also demonstrated longer duration of response (DoR), progression-free survival (PFS) and significant improvement in overall survival (OS) compared to IV administration during this time. Specifically, median DoR was numerically longer for SC amivantamab combined with lazertinib compared to IV (median, 11.2 vs 8.3 months among confirmed responders) as was PFS (median, 6.1 vs 4.3 months; hazard ratio [HR], 0.84; 95 percent CI, 0.64–1.10; P=0.20). A pre-specified exploratory endpoint showed patients treated with SC amivantamab had significantly longer OS compared with IV (HR, 0.62; 95 percent CI, 0.42–0.92; nominal P=0.02). At 12 months, 65 percent of patients who received SC amivantamab combined with lazertinib were alive compared with 51 percent of those treated with the IV regimen. It is theorized that the efficacy seen with SC amivantamab may be linked to SC absorption via the lymphatic system, potentially enhancing immune-mediated activity.1
Of particular note, administration time was substantially shorter for SC amivantamab (median less than approximately five minutes) compared to IV administration (up to five hours), with significantly more patients reporting convenience with the SC administration (85 percent with SC amivantamab vs 35 percent with IV administration at end of treatment; P