Abstract 1247P
Background
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.
Methods
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.
Results
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.
Conclusions
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
NCT02609776.
Editorial acknowledgement
Medical writing assistance was funded by Janssen Global Services, LLC. and provided by Tracy T. Cao, PhD (Janssen Global Services, LLC.).
Legal entity responsible for the study
Janssen.
Funding
Janssen.
Disclosure
K. Park: Financial Interests, Personal, Advisory Role: AstraZeneca, Lilly, Ono Pharmaceutical, Bristol Myers Squibb, MSD, Blueprint Medicines, Amgen, Merck KGaA, Loxo, AbbVie, Daiichi Sankyo, Boehringer Ingelheim, Johnson & Johnson, Eisai, Puma Biotechnology; Financial Interests, Personal, Speaker’s Bureau: Boehringer Ingelheim, AZD; Financial Interests, Personal, Funding: AstraZeneca, MSD Oncology. J.K. Sabari: Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen Oncology, Navire, Pfizer, Regeneron, Medscape, Takeda. E.B. Haura: Financial Interests, Personal, Advisory Role: Janssen Pharmaceuticals, Revolution Medicines, Ellipses Pharmaceuticals; Financial Interests, Institutional, Funding: Revolution Medicines. C.A. Shu: Financial Interests, Personal, Advisory Board: Genentech, AstraZeneca, Janssen, Mirati. A. Spira: Financial Interests, Personal and Institutional, Speaker’s Bureau: Janssen; Financial Interests, Personal, Advisory Board: Mirati, Amgen, Sanofi, Novartis, Incyte. K.L. Reckamp: Financial Interests, Personal, Advisory Role: Amgen, Tesaro, Boehringer Ingelheim, Takeda, AstraZeneca, Seattle Genetics, Calithera Biosciences, Genentech, Blueprint Medicines, Daiichi Sankyo/Lilly, EMD Serono, Janssen Oncology, Lilly, Merck KGaA; Financial Interests, Institutional, Funding: Bristol Myers Squibb, Pfizer, ARIAD, Xcovery, Adaptimmune, Genentech/Roche, Boehringer Ingelheim, AbbVie, ACEA Biosciences, Loxo, GlaxoSmithKline, Guardant Health, Janssen Oncology, Seattle Genetics, Zeno Pharmaceuticals, Calithera Biosciences, Elevation. R.E. Sanborn: Financial Interests, Personal, Advisory Role: Genentech/Roche, AstraZeneca, EMD Serono, Blueprint Medicines, Daiichi Sankyo, Lilly, Janssen Oncology; Financial Interests, Personal, Other, travel, accommodations, expenses: AstraZeneca; Financial Interests, Personal, Other, honoraria: AstraZeneca, Amgen; Financial Interests, Institutional, Funding: Bristol Myers Squibb, MedImmune; Financial Interests, Personal, Funding: Merck, AstraZeneca. J.M. Bauml: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, AstraZeneca, Genentech, Celgene, Boehringer Ingelheim, Guardant Health, Takeda, Novartis, Janssen, Ayala Pharmaceuticals, Regeneron, Inivata, Novartis, Foundation Medicine; Financial Interests, Institutional, Funding: Merck, Carevive Systems, Novartis, Incyte, Bayer, Janssen, AstraZeneca, Takeda, Amgen, Pfizer, Mirati Therapeutics. J.C. Curtin: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. J. Xie: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. A. Roshak: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. P. Lorenzini: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. D. Millington: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. M. Thayu: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. R.E. Knoblauch: Financial Interests, Personal, Full or part-time Employment: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson. B.C. Cho: Financial Interests, Personal and Institutional, Research Grant: Novartis, Bayer, AstraZeneca, Mogam Institute, Dong-A ST, Champions Oncology, Janssen, Yuhan, Ono, Dizal Pharma, MSD, AbbVie, Medpacto, GI Innovation, Eli Lilly, Blueprint Medicines, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Board: Kanaph Therapeutics Inc., BridgeBio Therapeutics, Cyrus therapeutics, Guardant Health; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc., Gencurix Inc., BridgeBio therapeutics, Kanaph Therapeutics Inc., Cyrus therapeutics, Interpark Bio Convergence Corp.; Financial Interests, Personal, Advisory Role: Novartis, AstraZeneca, Boehringer Ingelheim, Roche, BMS, Ono, Yuhan, Pfizer, Eli Lilly, Janssen, Takeda, MSD, Medpacto, Blueprint Medicines; Financial Interests, Personal, Member of the Board of Directors: Interpark Bio Convergence Corp.; Financial Interests, Personal, Royalties: Champions Oncology; Non-Financial Interests, Personal, Other, Founder: DAAN Biotherapeutics. All other authors have declared no conflicts of interest.