Janssen's SKIPPirr study reveals that a prophylactic regimen of dexamethasone significantly reduces infusion-related reactions (IRRs) in patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) treated with intravenous RYBREVANT® (amivantamab). The Phase 2 trial demonstrated a three-fold reduction in IRR incidence, offering a potential strategy to improve patient experience.
The open-label Phase 2 SKIPPirr study, included 40 patients and evaluated additional prophylactic strategies to reduce the incidence of infusion-related reactions (IRRs) with intravenous (IV) RYBREVANT® (amivantamab) in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) exon 19 deletions (ex19del) or L858R substitution mutations. The results were presented at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC).
Key Findings from the SKIPPirr Study
The SKIPPirr study focused on patients with EGFR exon 19 deletions or L858R substitution mutations who had progressed on osimertinib and platinum-based chemotherapy. The study met its primary endpoint, demonstrating that prophylaxis with 8 mg dexamethasone taken for two days prior to the first infusion resulted in an all-grades IRR rate for IV amivantamab of 22.5 percent at Cycle 1 Day 1 (C1D1). This is a significant reduction compared to the 67.4 percent IRR rate historically seen with standard management of IRRs with IV amivantamab.
Other arms of the study exploring different prophylactic regimens, including dexamethasone 4 mg, montelukast, and methotrexate, were stopped for futility.
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, 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."
Dosing and Safety Profile
In the study, patients received an at-home regimen of oral dexamethasone, taking an 8 mg dose twice daily on the two prior days and one dose one hour prior to receiving IV amivantamab, in addition to the standard prophylactic regimen. The amivantamab treatment was combined with lazertinib. All IRRs were Grade 1 or 2, with no patients requiring hospitalization due to IRRs. The safety profile of amivantamab and lazertinib with prophylactic dexamethasone at the initiation of treatment was consistent with previous studies. The most common IRR-related symptoms observed were nausea (8 percent), dyspnea (5 percent), and hypotension (5 percent).
Implications for NSCLC Treatment
Reducing the risk of IRRs is a critical aspect of improving the overall treatment experience for patients receiving intravenous amivantamab and oral lazertinib. By incorporating an additional treatment regimen of prophylactic oral dexamethasone, the risk can be mitigated, with the goal of allowing patients to continue their therapy with fewer interruptions.
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, and by harnessing the immune system. It is approved in Europe for specific indications of advanced NSCLC with EGFR exon 20 insertion mutations and in combination with chemotherapy for EGFR exon 19 deletions or L858R substitution mutations after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI).
