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

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Amivantamab, an EGFR-MET bispecific antibody, is approved for multiple indications in EGFR-mutated advanced non-small cell lung cancer (NSCLC) as monotherapy or combined with other agents. Intravenous amivantamab is associated with a 67% infusion-related reactions (IRR) rate. The phase 2 SKIPPirr study (NCT05663866) enrolled patients with EGFR-mutated (Ex19del/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, 4 independent prophylactic approaches were evaluated using Simon's 2-stage design with an expansion stage if a cohort passed both stages: oral dexamethasone 4-mg twice daily (BID) given on cycle (C) 1 day (D) -1; oral dexamethasone 8-mg BID given on C1D-2, C1D-1, and morning of C1D1 (5 doses); oral montelukast 10-mg once daily given on C1D-4, C1D-3, C1D-2, C1D-1, and C1D1 (5 doses); subcutaneous methotrexate 25-mg (1 dose) given anytime between C1D-7 and C1D-3. Primary endpoint was C1D1 IRR incidence. As of 24-June-2024, 68 patients were treated across all cohorts. The dexamethasone 8-mg cohort passed stages 1 and 2 proceeding to the expansion stage, with 24 additional patients treated. At C1D1, 9/40 patients (22.5%) experienced IRRs, resulting in an ∼3-fold decrease versus historical data (67.4%). By end of C3, 10/41 (24.4%) patients in the dexamethasone 8-mg cohort experienced IRRs (grades 1-2, except 1 grade 3 on C2D1). Amivantamab-lazertinib safety and efficacy were consistent with previous reports. Prophylaxis with 8-mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.