Preventing Infusion-Related Reactions With Intravenous Amivantamab-Results From SKIPPirr, a Phase 2 Study: A Brief Report.

introductionAmivantamab, an EGFR-MET bispecific antibody, is approved for multiple indications in EGFR-mutated advanced NSCLC as monotherapy or combined with other agents. Intravenous amivantamab is associated with a 67% infusion-related reaction (IRR) rate.

methodsThe phase 2 SKIPPirr study (NCT05663866) enrolled participants with EGFR-mutated (exon 19 deletion or exon 21 L858R) advanced NSCLC after progression on osimertinib and platinum-based chemotherapy who received intravenous amivantamab plus oral lazertinib (amivantamab-lazertinib), a third-generation tyrosine kinase inhibitor. Aiming to mitigate IRRs, four independent prophylactic approaches were evaluated using Simon's two-stage design with an expansion stage if a cohort passed both stages: oral dexamethasone 4 mg twice daily given on cycle (C) 1 day (D) -1 (two doses); oral dexamethasone 8 mg twice daily given on C1D-2, C1D-1, and the morning of C1D1 (five doses); oral montelukast 10 mg once daily given on C1D-4, C1D-3, C1D-2, C1D-1, and C1D1 (five doses); subcutaneous methotrexate 25 mg (one dose) given anytime between C1D-7 and C1D-3. The primary end point was C1D1 IRR incidence.

resultsAs of June 24, 2024, 68 participants were treated across all cohorts. The dexamethasone 8 mg cohort passed stages 1 and 2 proceeding to the expansion stage, with 24 additional participants treated. At C1D1, nine of 40 participants (22.5%) experienced IRRs, resulting in an approximately threefold decrease versus historical data (67.4%). By the end of C3, 10 of 41 participants (24.4%) in the dexamethasone 8 mg cohort experienced IRRs (grades 1-2, except one grade 3 on C2D1). Amivantamab-lazertinib's safety and efficacy were consistent with previous reports.

conclusionsProphylaxis with 8 mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.