PortalPublikationenPhase I study of tomuzotuximab, a glycoengineered therapeuti...

Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas

Standard

Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas. / Fiedler, Walter; Cresta, Sara; Schulze-Bergkamen, Henning; De Dosso, Sara; Weidmann, Jens; Tessari, Anna; Baumeister, Hans; Danielczyk, Antje; Dietrich, Bruno; Goletz, Steffen; Zurlo, Alfredo; Salzberg, Marc; Sessa, Cristiana; Gianni, Luca.

in: ESMO OPEN, Jahrgang 3, Nr. 2, 2018, S. e000303.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Fiedler, W, Cresta, S, Schulze-Bergkamen, H, De Dosso, S, Weidmann, J, Tessari, A, Baumeister, H, Danielczyk, A, Dietrich, B, Goletz, S, Zurlo, A, Salzberg, M, Sessa, C & Gianni, L 2018, 'Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas', ESMO OPEN, Jg. 3, Nr. 2, S. e000303. https://doi.org/10.1136/esmoopen-2017-000303

APA

Fiedler, W., Cresta, S., Schulze-Bergkamen, H., De Dosso, S., Weidmann, J., Tessari, A., Baumeister, H., Danielczyk, A., Dietrich, B., Goletz, S., Zurlo, A., Salzberg, M., Sessa, C., & Gianni, L. (2018). Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas. ESMO OPEN, 3(2), e000303. https://doi.org/10.1136/esmoopen-2017-000303

Vancouver

Fiedler W, Cresta S, Schulze-Bergkamen H, De Dosso S, Weidmann J, Tessari A et al. Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas. ESMO OPEN. 2018;3(2):e000303. https://doi.org/10.1136/esmoopen-2017-000303

Bibtex

@article{7a78744a6ae142828809505a46658008,
title = "Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas",
abstract = "Background: Changes in glycosylation of the constant domain (Fc) of monoclonal antibodies (mAbs) enhance antibody-dependent cell-mediated cytotoxicity independently of downstream effects following receptor blockade by the antibody, thus extending their indication. We investigated the safety, pharmacokinetics, pharmacodynamics and antitumour activity of tomuzotuximab, an IgG1 glycoengineered mAb against the epidermal growth factor receptor with enhanced tumour cytotoxicity in a phase I dose-escalation study (NTC01222637).Patients and methods: Forty-one patients with advanced solid tumours refractory to standard therapies received tomuzotuximab weekly (12-1370 mg) or two-weekly (990 mg) on a three-plus-three dose escalation design.Results: A maximum tolerated dose was not reached. The most frequent treatment-related adverse events were infusion-related reactions in 31 (76%) patients (grade 3, 12%), mainly confined to the first dose, and skin toxicities (grade 1 or 2) in 30 (73%) patients. Hypomagnesaemia was observed in 9 out of 23 evaluable patients (39%). Similar to cetuximab, tomuzotuximab concentrations increased proportionally to dose from doses≥480 mg with a median terminal half life (t½) of 82 hours, range 55-113 hours. Antitumour activity included one complete response ongoing since more than 4.5 years in a patient with non-small-cell lung cancer and one partial response lasting 353 days in a patient with colorectal cancer. Twelve patients achieved stable disease (median, 166 days, range, 71-414 days) and two patients had prolonged control (>1 year) of their non-measurable disease.Conclusion: Tomuzotuximab was safe and showed promising antitumour activity in heavily pretreated patients with advanced metastatic disease. A phase IIb trial of chemotherapy and weekly tomuzotuximab or cetuximab followed with maintenance therapy with the corresponding mAb in patients with recurrent or metastatic head and neck squamous cell carcinoma is ongoing.",
keywords = "Journal Article",
author = "Walter Fiedler and Sara Cresta and Henning Schulze-Bergkamen and {De Dosso}, Sara and Jens Weidmann and Anna Tessari and Hans Baumeister and Antje Danielczyk and Bruno Dietrich and Steffen Goletz and Alfredo Zurlo and Marc Salzberg and Cristiana Sessa and Luca Gianni",
year = "2018",
doi = "10.1136/esmoopen-2017-000303",
language = "English",
volume = "3",
pages = "e000303",
journal = "ESMO OPEN",
issn = "2059-7029",
publisher = "BMJ PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Phase I study of tomuzotuximab, a glycoengineered therapeutic antibody against the epidermal growth factor receptor, in patients with advanced carcinomas

AU - Fiedler, Walter

AU - Cresta, Sara

AU - Schulze-Bergkamen, Henning

AU - De Dosso, Sara

AU - Weidmann, Jens

AU - Tessari, Anna

AU - Baumeister, Hans

AU - Danielczyk, Antje

AU - Dietrich, Bruno

AU - Goletz, Steffen

AU - Zurlo, Alfredo

AU - Salzberg, Marc

AU - Sessa, Cristiana

AU - Gianni, Luca

PY - 2018

Y1 - 2018

N2 - Background: Changes in glycosylation of the constant domain (Fc) of monoclonal antibodies (mAbs) enhance antibody-dependent cell-mediated cytotoxicity independently of downstream effects following receptor blockade by the antibody, thus extending their indication. We investigated the safety, pharmacokinetics, pharmacodynamics and antitumour activity of tomuzotuximab, an IgG1 glycoengineered mAb against the epidermal growth factor receptor with enhanced tumour cytotoxicity in a phase I dose-escalation study (NTC01222637).Patients and methods: Forty-one patients with advanced solid tumours refractory to standard therapies received tomuzotuximab weekly (12-1370 mg) or two-weekly (990 mg) on a three-plus-three dose escalation design.Results: A maximum tolerated dose was not reached. The most frequent treatment-related adverse events were infusion-related reactions in 31 (76%) patients (grade 3, 12%), mainly confined to the first dose, and skin toxicities (grade 1 or 2) in 30 (73%) patients. Hypomagnesaemia was observed in 9 out of 23 evaluable patients (39%). Similar to cetuximab, tomuzotuximab concentrations increased proportionally to dose from doses≥480 mg with a median terminal half life (t½) of 82 hours, range 55-113 hours. Antitumour activity included one complete response ongoing since more than 4.5 years in a patient with non-small-cell lung cancer and one partial response lasting 353 days in a patient with colorectal cancer. Twelve patients achieved stable disease (median, 166 days, range, 71-414 days) and two patients had prolonged control (>1 year) of their non-measurable disease.Conclusion: Tomuzotuximab was safe and showed promising antitumour activity in heavily pretreated patients with advanced metastatic disease. A phase IIb trial of chemotherapy and weekly tomuzotuximab or cetuximab followed with maintenance therapy with the corresponding mAb in patients with recurrent or metastatic head and neck squamous cell carcinoma is ongoing.

AB - Background: Changes in glycosylation of the constant domain (Fc) of monoclonal antibodies (mAbs) enhance antibody-dependent cell-mediated cytotoxicity independently of downstream effects following receptor blockade by the antibody, thus extending their indication. We investigated the safety, pharmacokinetics, pharmacodynamics and antitumour activity of tomuzotuximab, an IgG1 glycoengineered mAb against the epidermal growth factor receptor with enhanced tumour cytotoxicity in a phase I dose-escalation study (NTC01222637).Patients and methods: Forty-one patients with advanced solid tumours refractory to standard therapies received tomuzotuximab weekly (12-1370 mg) or two-weekly (990 mg) on a three-plus-three dose escalation design.Results: A maximum tolerated dose was not reached. The most frequent treatment-related adverse events were infusion-related reactions in 31 (76%) patients (grade 3, 12%), mainly confined to the first dose, and skin toxicities (grade 1 or 2) in 30 (73%) patients. Hypomagnesaemia was observed in 9 out of 23 evaluable patients (39%). Similar to cetuximab, tomuzotuximab concentrations increased proportionally to dose from doses≥480 mg with a median terminal half life (t½) of 82 hours, range 55-113 hours. Antitumour activity included one complete response ongoing since more than 4.5 years in a patient with non-small-cell lung cancer and one partial response lasting 353 days in a patient with colorectal cancer. Twelve patients achieved stable disease (median, 166 days, range, 71-414 days) and two patients had prolonged control (>1 year) of their non-measurable disease.Conclusion: Tomuzotuximab was safe and showed promising antitumour activity in heavily pretreated patients with advanced metastatic disease. A phase IIb trial of chemotherapy and weekly tomuzotuximab or cetuximab followed with maintenance therapy with the corresponding mAb in patients with recurrent or metastatic head and neck squamous cell carcinoma is ongoing.

KW - Journal Article

U2 - 10.1136/esmoopen-2017-000303

DO - 10.1136/esmoopen-2017-000303

M3 - SCORING: Journal article

C2 - 29464112

VL - 3

SP - e000303

JO - ESMO OPEN

JF - ESMO OPEN

SN - 2059-7029

IS - 2

ER -