Johnson & Johnson has announced positive results from its Phase II SKIPPirr study, evaluating the combination of intravenous Rybrevant (amivantamab-vmjw) and oral Lazcluze in patients with non-small cell lung cancer (NSCLC). The study focused on reducing infusion-related reactions (IRRs) through a prophylactic dexamethasone regimen.
The open-label trial enrolled 40 patients with advanced NSCLC harboring epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations, all of whom had experienced disease progression following treatment with osimertinib and platinum-based chemotherapy. All participants received both oral Lazcluze and IV Rybrevant.
Dexamethasone Prophylaxis Reduces IRR Incidence
The primary endpoint of the study, the incidence of IRRs, was successfully met. Data indicated that administering an 8mg dose of dexamethasone twice daily for two days before the first Rybrevant infusion significantly lowered the IRR rate to 22.5% at Cycle 1 Day 1. This is a notable improvement compared to the historical IRR incidence rate of 67.4% observed with standard management protocols.
Patients followed an at-home regimen, taking 8mg of oral dexamethasone twice daily for two days before and one hour prior to each intravenous Rybrevant administration.
Safety Profile and Tolerability
The treatment combination, including prophylactic dexamethasone, resulted in all IRRs being Grade 1 or 2, with no patients requiring hospitalization. Furthermore, the study reported no Grade 3 or higher IRR events.
The safety profile of Rybrevant and Lazcluze, when initiated with prophylactic dexamethasone, aligned with findings from prior studies. No significant increase in adverse events was observed. Reported symptoms related to IRRs included nausea, dyspnea, and hypotension.
Mechanism of Action and Prior Approvals
Rybrevant, a fully human bispecific antibody, targets both EGFR and MET with immune cell-directing activity. It is currently approved in several markets as a monotherapy for adult patients with locally advanced or metastatic NSCLC exhibiting EGFR exon 20 insertion mutations, specifically those whose disease has progressed after platinum-based chemotherapy.
Expert Commentary
Mark Wildgust, Vice President of Innovative Medicine Oncology Global Medical Affairs at Johnson & Johnson, stated, “Reducing the risk of IRRs is a critical aspect of improving the overall treatment experience for patients receiving intravenous RYBREVANT and oral LAZCLUZE. Incorporating oral dexamethasone into the treatment regimen suggests we can help mitigate this risk, with the goal of allowing patients to continue their therapy with fewer interruptions.”
