Safety and tolerability of AMG 330 in adults with relapsed/refractory AML: a phase 1a dose-escalation study

Abstract

AMG 330, a bispecific T-cell engager (BiTE®) that binds CD33 and CD3 on T cells facilitates T-cell–mediated cytotoxicity against CD33+ cells. This first-in-human, open-label, dose-escalation study evaluated the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of AMG 330 in adults with relapsed/refractory acute myeloid leukemia (R/R AML). Amongst 77 patients treated with AMG 330 (0.5 µg/day–1.6 mg/day) on 14-day or 28-day cycles, maximum tolerated dose was not reached; median duration of treatment was 29 days. The most frequent treatment-related adverse events were cytokine release syndrome (CRS; 78%) and rash (30%); 10% of patients experienced grade 3/4 CRS. CRS was mitigated with stepwise dosing of AMG 330, prophylactic dexamethasone, and early treatment with tocilizumab. Among 60 evaluable patients, eight achieved complete remission or morphologic leukemia-free state; of the 52 non-responders, 37% had ≥50% reduction in AML bone marrow blasts. AMG 330 is a promising CD33-targeted therapeutic strategy for R/R AML.

Keywords:

• AML
• BiTE®
• CD33
• CRS
• dose-escalation
• interleukin
• T-cell

Acknowledgments

Medical writing/editorial support was provided by Lisa R. Denny, PhD, and Lee B. Hohaia, PharmD (ICON, Blue Bell, PA), and Manoj Kumar Goyal, PhD of Cactus Life Sciences (part of Cactus Communications) and funded by Amgen Inc.

Authors’ contributions

Contribution: P.K.Y., L.M., B.P., M.R.Y., S.A., and S.K.K. contributed to study design, collection, analysis and interpretation of the data. F.R., M.S., R.B.W., P.V., G.O., V.B., H.D., M.J.-L., C.D.B., L.F., T.S.P., H.K., and A.S. contributed to this study by enrolling patients, conducting treatments, collecting samples, assessing safety and efficacy of AMG 330, providing feedback on study design, and analysis and interpretation of data. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Qualified researchers may request deidentified data from Amgen clinical studies; complete details are available at http://www.amgen.com/datasharing.

Additional information

Funding

P.K.Y., L.M., B.P., and M.R.Y. report employment with and stock/stock options in Amgen Inc. S.A., and S.K.K. report employment with Amgen Inc. F.R. has received research support and consultation fee from Amgen Inc. M.S. has received consultation fees and/or served on advisory board for AbbVie, Advesya, Amgen Inc., Autolus, AvenCell, BMS/Celgene, Genmab US, Gilead Sciences, Kite, Ichnos Sciences, InCyte Biosciences, Interius BioTherapeutics, Janssen, Miltenyi, Molecular Partner, Nectar Therapeutics, Novartis, Orbital Therapeutics, Pfizer, Roche, Sanofi, Skare and Takeda; served on the speakers’ bureau for AstraZeneca, GlaxoSmithKline (GSK), BMS/Celgene, Gilead Sciences/Kite, Janssen, LAWG, Novartis, Pfizer, Roche and Springer Healthcare; received travel, accommodations, and expenses from Kite, Pfizer, Roche, and Gilead Sciences; and received research support from Amgen Inc., BMS/Celgene, Gilead Sciences, Kite, MiltenyiBiotec, Molecular Partner, Novartis, Roche, Takeda, and Seattle Genetics. R.B.W. received laboratory research grants and/or clinical trial support from Amgen Inc., Aptevo, BMS, Celgene, ImmunoGen, Janssen, Jazz, Kura, MacroGenics, Pfizer and VOR; has ownership interests in Amphivena; and is (or has been) a consultant to AbbVie, Adicet, Amphivena, BerGenBio, BMS, Celgene, GSK, ImmunoGen, Kura, Wugen, and Orum. P.V. reports consulting-related honorarium from AbbVie, Amgen Inc., Blueprint Medicines, Cogent Biosciences, Incyte, CTI BioPharma Corp, Daiichi Sankyo, GSK, Merck, Novartis, Pfizer, Genentech, Servier, Stemline, MorphoSys and LAVA Therapeutics.V.B. received research grants from BMS, Novartis, Takeda and Roche; served as consultant/advisor to Amgen, Gilead, Novartis, Pfizer, and Priothera; serves on the speakers’ bureau at Novartis and Pfizer. H.D. reports advisory role for AbbVie, AstraZeneca, Gilead, Janssen, Jazz Pharmaceuticals, Syndax Pfizer, Servier, and Stemline; has received research funding from Abbvie, Astellas, BMS, Jazz, Kronos, and Servier. G.O., and M.J.-L. report nothing to disclose. C.D.B. has received travel, accommodations, and expenses from and served on advisory board, speakers’ bureau for Amgen Inc., JAZZ, BMS, AbbVie, Gilead Sciences, Janssen, Astellas, AstraZeneca, and Pfizer. L.F reports consultancy for Amgen Germany GmbH. T.S.P. reports research grant from Delta Fry Pharmaceuticals and consulting for AstraZeneca, AbbVie, and Genentech. H.K. has received research funding from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, and Novartis; and received honoraria from AbbVie, Amgen, Ascentage, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Shenzhen Target Rx, Stemline, and Takeda. A.S. received consultation fee from Syndax and served on the speakers’ bureau for Amgen Inc.