Preventing Infusion-Related Reactions With Intravenous Amivantamab-Results From SKIPPirr, a Phase 2 Study: A Brief Report.
Journal
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
ISSN
1556-1380
Date Issued
2025-01-24
Author(s)
Spira, Alexander I
Paz-Ares, Luis
Han, Ji-Youn
Mascaux, Céline
Roy, Upal Basu
Zugazagoitia, Jon
Kim, Yu Jung
Chiu, Chao-Hua
Kim, Sang-We
Nadal, Ernest
Gil-Bazo, Ignacio
Murphy, Sean P
Anderson, Bailey G
Xia, Yichuan
Wang, George
Bauml, Joshua M
Chioda, Marc
Simoes, Jairo
Mahadevia, Parthiv J
Lopes, Gilberto
Abstract
Introduction: Amivantamab, 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. Methods: The 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. Results: As 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. Conclusions: Prophylaxis with 8 mg oral dexamethasone meaningfully reduced IRRs and can be readily implemented in clinical practice.
Subjects
Amivantamab
Dexamethasone
Infusion-related reactions
NSCLC
Prophylaxis
Type
journal article