Johnson & Johnson announced results from the Phase 2 SKIPPirr study, revealing that dexamethasone significantly reduces infusion-related reactions (IRRs) in patients with EGFR-mutated non-small cell lung cancer (NSCLC) treated with intravenous RYBREVANT® (amivantamab-vmjw). The study, presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC), offers a potential strategy to improve patient experience with amivantamab treatment.
The open-label Phase 2 study (NCT05663866) included 40 patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. Patients received an at-home regimen of oral dexamethasone, taking an 8-mg dose twice daily on the two prior days and one hour prior to receiving IV RYBREVANT® in combination with LAZCLUZE™ (lazertinib).
Key Findings from the SKIPPirr Study
The primary endpoint of the study, incidence of IRRs at Cycle 1 Day 1 (C1D1), was met, with an all-grades IRR rate for IV RYBREVANT® of 22.5 percent. This represents a three-fold reduction in the incidence of IRRs compared to standard management of IRRs with IV RYBREVANT®, where historic data has observed an all-grades incidence rate of 67.4 percent.
All IRRs were Grade 1 or 2, and no patients required hospitalization due to IRRs. There were no Grade 3 or higher IRR events reported. The safety profile of RYBREVANT® and LAZCLUZE™ with prophylactic dexamethasone at the initiation of treatment was consistent with previous studies, showing no significant increase in adverse events. The most common IRR-related symptoms observed in the study were nausea (8 percent), dyspnea (5 percent) and hypotension (5 percent).
Expert Commentary
"These data offer important insights that may help improve the patient experience with intravenous amivantamab treatment," said Gilberto Lopes, M.D., associate director of global oncology at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and presenting author. "This study shows us that an easily accessible approach of an increased dose regimen of dexamethasone as a pre-treatment prophylaxis can potentially help lower IRRs. It is encouraging to see a three-fold decrease in IRRs, when comparing the rates in SKIPPirr to historical data."
Implications for Clinical Practice
The findings suggest that incorporating oral dexamethasone into the treatment regimen can mitigate the risk of IRRs, potentially allowing patients to continue their therapy with fewer interruptions. Mark Wildgust, Ph.D., Vice President of Oncology Global Medical Affairs, Johnson & Johnson Innovative Medicine, emphasized that reducing the risk of IRRs is a critical aspect of improving the overall treatment experience for patients receiving intravenous RYBREVANT and oral LAZCLUZE.
Ongoing Research
Johnson & Johnson is continuing to evaluate prophylactic strategies to reduce IRRs for patients receiving IV RYBREVANT® in additional studies. RYBREVANT® is also being studied in multiple clinical trials in NSCLC, including the Phase 3 MARIPOSA, MARIPOSA-2, PAPILLON, and PALOMA-3 studies.
