AMG 757, a Half-Life Extended, DLL3-Targeted Bispecific T-Cell Engager, Shows High Potency and Sensitivity in Preclinical Models of Small-Cell Lung Cancer.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Michael J GiffinPaul E Hughes

Abstract

Small-cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with a high relapse rate, limited therapeutic options, and poor prognosis. We investigated the antitumor activity of AMG 757, a half-life extended bispecific T-cell engager molecule targeting delta-like ligand 3 (DLL3)-a target that is selectively expressed in SCLC tumors, but with minimal normal tissue expression. AMG 757 efficacy was evaluated in SCLC cell lines and in orthotopic and patient-derived xenograft (PDX) mouse SCLC models. Following AMG 757 administration, changes in tumor volume, pharmacodynamic changes in tumor-infiltrating T cells (TILs), and the spatial relationship between the appearance of TILs and tumor histology were examined. Tolerability was assessed in nonhuman primates (NHPs). AMG 757 showed potent and specific killing of even those SCLC cell lines with very low DLL3 expression (<1,000 molecules per cell). AMG 757 effectively engaged systemically administered human T cells, induced T-cell activation, and redirected T cells to lyse tumor cells to promote significant tumor regression and complete responses in PDX models of SCLC and in orthotopic models of established primary lung SCLC and metastatic liver lesions. AMG 757 was well tolerat...Continue Reading

References

Oct 11, 2005·Drug Discovery Today·Evelyn WolfPatrick A Baeuerle
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ramaswamy GovindanJay Piccirillo
Aug 1, 2007·The Journal of Cell Biology·Insa GeffersAchim Gossler
Oct 23, 2014·Cancer·Lauren Averett Byers, Charles M Rudin
Jul 17, 2015·Cancer Research·John W CassidyAlejandra Bruna
Sep 10, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Charles M RudinGiuseppe Giaccone
Feb 18, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Maria-Elisabeth GoebelerRalf C Bargou
Dec 21, 2016·The Journal of Biological Chemistry·Frederick W JacobsenKannan Gunasekaran
Mar 2, 2017·The New England Journal of Medicine·Hagop KantarjianMax S Topp
May 11, 2017·Cancer Research·Sai Kiran SharmaJason S Lewis
May 24, 2017·Nature Reviews. Clinical Oncology·Joshua K SabariCharles M Rudin
Aug 17, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick A OttJanice M Mehnert
Oct 28, 2017·Nature Reviews. Cancer·Adi F GazdarJohn D Minna
Jan 13, 2018·Endocrine-related Cancer·Atsuko KasajimaWilko Weichert
Apr 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Eunseon AhnRafi Ahmed
Oct 4, 2018·The New England Journal of Medicine·Leora HornUNKNOWN IMpower133 Study Group
Oct 14, 2018·Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer·Neal ReadyScott J Antonia
Jun 20, 2019·Journal of Hematology & Oncology·Dwight H OwenKai He
Sep 12, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Daniel MorgenszternDavid P Carbone
Jan 3, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Max S ToppHermann Einsele

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Citations

Jan 29, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Petra DeegenJulie M Bailis
Jul 23, 2021·Nature Reviews. Urology·Yong WangYuzhuo Wang
Aug 11, 2021·Expert Review of Respiratory Medicine·Andrea BiancoDanilo Rocco
Aug 13, 2021·Biochemistry and Biophysics Reports·Kazuo OharaMiki Ando
Aug 12, 2021·Molecular Cancer Therapeutics·Elizabeth PhamJulie M Bailis

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