1247P - Management of infusion-related reactions (IRRs) in patients receiving amivantamab
ESMO Congress 2021:ePoster Display
oregon; portland; chiles
Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, has shown antitumor activity in diverse EGFR and MET-driven non-small cell lung cancer (NSCLC), with safety consistent with associated on-target activities. IRRs are characteristic of antibody infusions, and have been described for other therapeutic antibodies. We review IRR and its management in patients (pts) treated with amivantamab.
CHRYSALIS is an ongoing phase I dose escalation/expansion study of amivantamab in advanced EGFR mutant NSCLC (NCT02609776). This report includes pts treated at the recommended phase II dose (RP2D) of 1050 mg IV amivantamab (1400 mg, ≥80 kg). Mitigations for IRR included split first dose (350 mg on day 1, remainder on day 2), reduced initial infusion rates with proactive infusion interruption, and required steroid premedication for the initial dose. For all doses, pre-infusion antihistamines and antipyretics were required; steroids were optional after initial dose.
As of 8 Jun 2020, 258 pts have received amivantamab at the RP2D. IRR was reported in 167 pts (65%) and was characterized by dyspnea, flushing, chills, and nausea. IRR severity was mostly grade 1–2; grade 3 IRR occurred in 5 pts, and 1 had a grade 4 event. Median time to IRR onset was 44 mins, with 94% occurring on cycle 1, day 1 (C1D1); only 1 event occurred ≥C2. Of the 167 pts with IRR, 134 completed the full split dose and continued treatment per schedule; 33 pts (13%) aborted C1D1 infusion due to IRR, of which 4 discontinued further therapy. Per protocol, IRRs were mitigated on C1D1 with holding of infusion (54%) and reinitiating at a reduced rate (50%). Translational studies in a subset of pts measuring 22 circulating analytes (e.g., markers of cytokine release syndrome, mast cell degranulation, tumor lysis syndrome, complement activation) failed to distinguish a pattern between pts with and without IRR.
IRRs with amivantamab treatment were frequently observed but were mostly low grade, primarily limited to the first infusion, and rarely occurred with subsequent dosing. Close monitoring for IRR with the initial dose helps mitigate IRR through proactive rate modifications.
Clinical trial identification
Earle A. Chiles Research Institute
Park, K; Sabari, JK; Haura, EB; Shu, CA; Spira, A; Salgia, R; Reckamp, KL; Sanborn, Rachel E; Govindan, R; Bauml, JM; Curtin, JC; Xie, J; Roshak, A; Lorenzini, P; Millington, D; Thayu, M; Knoblauch, RE; and Cho, BC, "1247P - Management of infusion-related reactions (IRRs) in patients receiving amivantamab" (2021). Articles, Abstracts, and Reports. 5369.