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Clinical Trial
. 2025 Jun;20(6):809-816.
doi: 10.1016/j.jtho.2025.01.018. Epub 2025 Jan 24.

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

Alexander I Spira  1 , Luis Paz-Ares  2 , Ji-Youn Han  3 , Jin-Yuan Shih  4 , Céline Mascaux  5 , Upal Basu Roy  6 , Jon Zugazagoitia  2 , Yu Jung Kim  7 , Chao-Hua Chiu  8 , Sang-We Kim  9 , Ernest Nadal  10 , Ignacio Gil-Bazo  11 , Sean P Murphy  12 , Bailey G Anderson  12 , Yichuan Xia  13 , George Wang  13 , Joshua M Bauml  13 , Marc Chioda  12 , Jairo Simoes  12 , Parthiv J Mahadevia  12 , Gilberto Lopes  14
Affiliations
Free article
Clinical Trial

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

Alexander I Spira et al. J Thorac Oncol. 2025 Jun.
Free article

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.

Keywords: Amivantamab; Dexamethasone; Infusion-related reactions; NSCLC; Prophylaxis.

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Conflict of interest statement

Disclosure Dr. Spira reports serving in a consulting or advisory role for Array Biopharma, Incyte, Amgen, Novartis, AstraZeneca, MedImmune, Mirati Therapeutics, Gritstone Bio, Jazz Pharmaceuticals, Merck, Bristol Myers Squibb, Janssen, Mersana, Blueprint Medicines, Daiichi Sankyo, Regeneron, Eli Lilly, Black Diamond Therapeutics, and Sanofi; serving in a leadership role for Next Oncology; owning stock or other ownership interest with Eli Lilly; receiving payment or honoraria from CytomX Therapeutics, AstraZeneca, Merck, Takeda, Amgen, Janssen, Novartis, Bristol Myers Squibb, and Bayer; receiving research funding from Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Incyte, AbbVie, Ignyta, Takeda, Macrogenics, CytomX Therapeutics, LAM Therapeutics, Astex Pharmaceuticals, Bristol Myers Squibb, Loxo Oncology, Arch Therapeutics, Gritstone Bio, Plexxikon, Amgen, Daiichi Sankyo, ADC Therapeutics, Janssen, Mirati Therapeutics, Rubius Therapeutics, Synthekine, Mersana, Blueprint Medicines, Regeneron, Alkermes, Revolution Medicines, Medikine, Black Diamond Therapeutics, BluPrint Oncology, Nalo Therapeutics, Scorpion Therapeutics, and ArriVent Biopharma. Dr. Paz-Ares reports serving in a consulting or advisory role for Roche, Merck Sharp & Dohme, Merck Serono, Bristol Myers Squibb, AstraZeneca, Eli Lilly, Pfizer, Pharmamar, Bayer, Amgen, Janssen, GlaxoSmithKline, Novartis, Takeda, Sanofi, Mirati, Genomica, Altum Sequencing, BeiGene, Daichii Sankyo, Medscape, and PER; serving as a member of the Board of Directors for Stab Therapeutics; receiving research funding from Daiichi Sankyo, AstraZeneca, Merck Sharp & Dohme, Bristol Myers Squibb, Janssen, Novartis, Roche, Sanofi, Amgen, Tesaro, Alkermes, Eli Lilly, Takeda, Pfizer, and Pharmamar. Dr. Han reports serving in a consulting or advisory role for Merck, AbbVie, AstraZeneca, Amgen, Daiichi Sankyo, LG Chem, Oncovix, Dae Woong, Novartis, Lantern, Bristol Myers Squibb, Janssen, Takeda, Pfizer, and Roche; receiving payment or honoraria from AstraZeneca, Janssen, Takeda, Merck, Novartis, Pfizer, Yuhan, and Roche; receiving payment for expert testimony from AstraZeneca; serving on a Data Safety Monitoring Board or Advisory Board for Janssen and AstraZeneca. Dr. Shih reports receiving payment or honoraria from ACTgenomics, Amgen, Genconn Biotech, AstraZeneca, Roche, Bayer, Boehringer Ingelheim, Eli Lilly, Pfizer, Novartis, Merck Sharp & Dohme, Chugai Pharma, Daiichi Sankyo, Takeda, CStone Pharmaceuticals, Janssen, TTY Biopharm, Orient EuroPharma, MundiPharma, GlaxoSmithKline, Lotus Pharmaceutical, Ono Pharmaceutical, and Bristol Myers Squibb; receiving support for attending meetings and/or travel from AstraZeneca, Roche, and Chugai Pharma; serving on a Data Safety Monitoring Board or Advisory Board for Takeda; receiving grants or contracts from Roche and Genconn Biotech. Dr. Mascaux reports serving in a consulting or advisory role for AstraZeneca, Roche, Merck Sharp & Dohme, Sanofi, Pfizer, Takeda, Janssen, and Amgen; receiving payment or honoraria from AstraZeneca, Roche, Merck Sharp & Dohme, Amgen, Pfizer, Takeda, Bristol Myers Squibb, and Sanofi; receiving support for attending meetings and/or travel for Janssen, Merck Sharp & Dohme, Takeda, Bristol Myers Squibb, Novartis, and Amgen. Dr. Roy reports serving in a consulting or advisory role for Janssen. Dr. Zugazagoitia reports receiving grants or contracts from AstraZeneca, Roche, and Bristol Myers Squibb; serving in a consulting or advisory role for Bristol Myers Squibb, Sanofi, and Pfizer; receiving payment or honoraria from Janssen, Takeda, Sanofi, Roche, AstraZeneca, NanoString, Amgen, Bristol Myers Squibb, Pfizer, Merck Sharp & Dohme, and Diagnostica Longwood; receiving support for attending meetings and/or travel from Janssen, Sanofi, AstraZeneca, Takeda, and Roche. Dr. Chiu reports receiving payment or honoraria from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceuticals, Daiichi Sankyo, Eli Lilly, Janssen, Merck KGaA, Merck Sharp & Dohme, Novartis, Ono Pharmaceutical, Pfizer, Roche, Shionogi, and Takeda; serving on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Merck KGaA, Novartis, Ono Pharmaceutical, and Roche. Dr. Nadal reports serving in a consulting or advisory role for Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Pfizer, Eli Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, and Qiagen; receiving grants of contracts from Roche, Bristol Myers Squibb, and Pfizer; receiving payment or honoraria from Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Sanofi, Pfizer, Eli Lilly, Amgen, Janssen, Daiichi Sankyo, Boehringer Ingelheim, AstraZeneca, Takeda, Sanofi, Pierre Fabre, Qiagen, and Bayer; receiving support for attending meetings and/or travel from Johnson & Johnson, Merck Sharp & Dohme, Takeda, and Roche; serving on a Data Safety Monitoring Board or Advisory Board for Roche, Apollomics, Merck Sharp & Dohme, and Transgene; serving in a leadership role for the Steering Committee of the Spanish Group of Lung Cancer (GECP). Dr. Gil-Bazo reports serving in a consulting or advisory role for Johnson & Johnson, Eli Lilly, and Boehringer Ingelheim; receiving payment or honoraria from Johnson & Johnson, Amgen, AstraZeneca, Merck Sharp & Dohme, and Takeda; receiving support for attending meetings and/or travel from Johnson & Johnson, Merck Sharp & Dohme, Daiichi Sankyo, and Sanofi. Sean P. Murphy, Bailey G. Anderson, Dr. Xia, George Wang, Dr. Bauml, Dr. Chioda, Dr. Simoes, and Dr. Mahadevia report being employed by (or were at the time of the study) and may hold stock in Johnson & Johnson, outside of the current work. Dr. Lopes reports serving in a consulting or advisory role for Pfizer and AstraZeneca; owning stock or other ownership interests with Lucence Diagnostics, Xilis, Biomab, Morphometrix, and CDR-Life; receiving payment or honoraria from Boehringer Ingelheim, Blueprint Medicines, AstraZeneca, Merck, and Janssen; receiving research funding from AstraZeneca, Lucence, Xilis, E.R. Squibb Sons, Merck Sharp & Dohme, EMD Serono, AstraZeneca, Blueprint Medicines, Tesaro, Bavarian Nordic, Novartis, G1 Therapeutics, Adaptimmune, Bristol Myers Squibb, GlaxoSmithKline, AbbVie, Rgenix, Pfizer, Roche, Genentech, Eli Lilly, and Janssen; receiving support for attending meetings and/or travel from Boehringer Ingelheim, Pfizer, E.R. Squibb Sons, Janssen, Seattle Genetics, Celgene, Ibsen, Pharmacyclics, Merck, AstraZeneca, and Seagen; and having other relationships with Mirati Therapeutics. The remaining authors declare no conflict of interest.

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