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A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors
We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion i...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136859/ https://www.ncbi.nlm.nih.gov/pubmed/30221040 http://dx.doi.org/10.1080/2162402X.2018.1450710 |
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author | Kebenko, Maxim Goebeler, Marie-Elisabeth Wolf, Martin Hasenburg, Annette Seggewiss-Bernhardt, Ruth Ritter, Barbara Rautenberg, Beate Atanackovic, Djordje Kratzer, Andrea Rottman, James B. Friedrich, Matthias Vieser, Eva Elm, Stefanie Patzak, Ingrid Wessiepe, Dorothea Stienen, Sabine Fiedler, Walter |
author_facet | Kebenko, Maxim Goebeler, Marie-Elisabeth Wolf, Martin Hasenburg, Annette Seggewiss-Bernhardt, Ruth Ritter, Barbara Rautenberg, Beate Atanackovic, Djordje Kratzer, Andrea Rottman, James B. Friedrich, Matthias Vieser, Eva Elm, Stefanie Patzak, Ingrid Wessiepe, Dorothea Stienen, Sabine Fiedler, Walter |
author_sort | Kebenko, Maxim |
collection | PubMed |
description | We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): eight had transient abnormal liver parameters shortly after infusion start or dose escalation (grade 3, n = 4; grade 4, n = 4), and one had supraventricular tachycardia (grade 3); all events resolved with solitomab discontinuation. Six patients had a DLT of diarrhea: four events resolved (grade 3, n = 3; grade 4, n = 1), one (grade 3) was ongoing at the time of treatment-unrelated death, and one (grade 3) progressed to grade 5 after solitomab discontinuation. The maximum tolerated dose was 24 µg/day. Overall, 95% of patients had grade ≥3 treatment-related AEs, primarily diarrhea, elevated liver parameters, and elevated lipase. Solitomab half-life was 4.5 hours; serum levels plateaued within 24 hours. One unconfirmed partial response was observed. In this study of a BiTE® antibody construct targeting solid tumors, treatment of relapsed/refractory EpCAM-positive solid tumors with solitomab was associated with DLTs, including severe diarrhea and increased liver enzymes, which precluded dose escalation to potentially therapeutic levels. |
format | Online Article Text |
id | pubmed-6136859 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-61368592018-09-14 A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors Kebenko, Maxim Goebeler, Marie-Elisabeth Wolf, Martin Hasenburg, Annette Seggewiss-Bernhardt, Ruth Ritter, Barbara Rautenberg, Beate Atanackovic, Djordje Kratzer, Andrea Rottman, James B. Friedrich, Matthias Vieser, Eva Elm, Stefanie Patzak, Ingrid Wessiepe, Dorothea Stienen, Sabine Fiedler, Walter Oncoimmunology Original Research We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): eight had transient abnormal liver parameters shortly after infusion start or dose escalation (grade 3, n = 4; grade 4, n = 4), and one had supraventricular tachycardia (grade 3); all events resolved with solitomab discontinuation. Six patients had a DLT of diarrhea: four events resolved (grade 3, n = 3; grade 4, n = 1), one (grade 3) was ongoing at the time of treatment-unrelated death, and one (grade 3) progressed to grade 5 after solitomab discontinuation. The maximum tolerated dose was 24 µg/day. Overall, 95% of patients had grade ≥3 treatment-related AEs, primarily diarrhea, elevated liver parameters, and elevated lipase. Solitomab half-life was 4.5 hours; serum levels plateaued within 24 hours. One unconfirmed partial response was observed. In this study of a BiTE® antibody construct targeting solid tumors, treatment of relapsed/refractory EpCAM-positive solid tumors with solitomab was associated with DLTs, including severe diarrhea and increased liver enzymes, which precluded dose escalation to potentially therapeutic levels. Taylor & Francis 2018-04-18 /pmc/articles/PMC6136859/ /pubmed/30221040 http://dx.doi.org/10.1080/2162402X.2018.1450710 Text en © 2018 The Author(s). Published with Taylor & Francis Group. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Original Research Kebenko, Maxim Goebeler, Marie-Elisabeth Wolf, Martin Hasenburg, Annette Seggewiss-Bernhardt, Ruth Ritter, Barbara Rautenberg, Beate Atanackovic, Djordje Kratzer, Andrea Rottman, James B. Friedrich, Matthias Vieser, Eva Elm, Stefanie Patzak, Ingrid Wessiepe, Dorothea Stienen, Sabine Fiedler, Walter A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title | A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title_full | A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title_fullStr | A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title_full_unstemmed | A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title_short | A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refractory solid tumors |
title_sort | multicenter phase 1 study of solitomab (mt110, amg 110), a bispecific epcam/cd3 t-cell engager (bite®) antibody construct, in patients with refractory solid tumors |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136859/ https://www.ncbi.nlm.nih.gov/pubmed/30221040 http://dx.doi.org/10.1080/2162402X.2018.1450710 |
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