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Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours

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Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. / Fiedler, Walter; Stoeger, Herbert; Perotti, Antonella; Gastl, Guenther; Weidmann, Jens; Dietrich, Bruno; Baumeister, Hans; Danielczyk, Antje; Goletz, Steffen; Salzberg, Marc; De Dosso, Sara.

In: ESMO OPEN, Vol. 3, No. 4, 2018, p. e000381.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Fiedler, W, Stoeger, H, Perotti, A, Gastl, G, Weidmann, J, Dietrich, B, Baumeister, H, Danielczyk, A, Goletz, S, Salzberg, M & De Dosso, S 2018, 'Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours', ESMO OPEN, vol. 3, no. 4, pp. e000381. https://doi.org/10.1136/esmoopen-2018-000381

APA

Fiedler, W., Stoeger, H., Perotti, A., Gastl, G., Weidmann, J., Dietrich, B., Baumeister, H., Danielczyk, A., Goletz, S., Salzberg, M., & De Dosso, S. (2018). Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. ESMO OPEN, 3(4), e000381. https://doi.org/10.1136/esmoopen-2018-000381

Vancouver

Fiedler W, Stoeger H, Perotti A, Gastl G, Weidmann J, Dietrich B et al. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. ESMO OPEN. 2018;3(4):e000381. https://doi.org/10.1136/esmoopen-2018-000381

Bibtex

@article{5d5d9fca703745559666cdc9933829f5,
title = "Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours",
abstract = "Purpose: TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies and to define the safety, pharmacokinetics (PK) and preliminary antitumour activity of TrasGEX.Patients and methods: A total of 37 patients with advanced HER2-positive carcinomas and progressive disease received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose.Results: No dose limiting toxicity was observed, and no maximum tolerated dose was reached. Drug-related adverse events were mainly infusion-related reactions occurring during the first infusion in 51% of patients; all but two were mild-to-moderate. Compared with trastuzumab, the PK parameters were dose dependent, with a mean terminal half-life (t1/2) of 263±99 hours for the 720 mg dose. Clinical benefit in 15 out of 30 (50%) evaluable patients included one ongoing complete response, two partial remissions lasting 16 and 77 weeks and disease stabilisation (SD) in 12 patients lasting a median (range) of 17 (7-26) weeks; three of them had SD of 24, 25 and 26 weeks, respectively.Conclusion: TrasGEX was safe, well-tolerated and showed antitumour activity in 50% of evaluable patients, all with progressive disease at study entry. Infusions at an interval of 2-3 weeks should achieve clinically relevant trough levels for future studies (NCT01409343).",
keywords = "Journal Article",
author = "Walter Fiedler and Herbert Stoeger and Antonella Perotti and Guenther Gastl and Jens Weidmann and Bruno Dietrich and Hans Baumeister and Antje Danielczyk and Steffen Goletz and Marc Salzberg and {De Dosso}, Sara",
year = "2018",
doi = "10.1136/esmoopen-2018-000381",
language = "English",
volume = "3",
pages = "e000381",
journal = "ESMO OPEN",
issn = "2059-7029",
publisher = "BMJ PUBLISHING GROUP",
number = "4",

}

RIS

TY - JOUR

T1 - Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours

AU - Fiedler, Walter

AU - Stoeger, Herbert

AU - Perotti, Antonella

AU - Gastl, Guenther

AU - Weidmann, Jens

AU - Dietrich, Bruno

AU - Baumeister, Hans

AU - Danielczyk, Antje

AU - Goletz, Steffen

AU - Salzberg, Marc

AU - De Dosso, Sara

PY - 2018

Y1 - 2018

N2 - Purpose: TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies and to define the safety, pharmacokinetics (PK) and preliminary antitumour activity of TrasGEX.Patients and methods: A total of 37 patients with advanced HER2-positive carcinomas and progressive disease received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose.Results: No dose limiting toxicity was observed, and no maximum tolerated dose was reached. Drug-related adverse events were mainly infusion-related reactions occurring during the first infusion in 51% of patients; all but two were mild-to-moderate. Compared with trastuzumab, the PK parameters were dose dependent, with a mean terminal half-life (t1/2) of 263±99 hours for the 720 mg dose. Clinical benefit in 15 out of 30 (50%) evaluable patients included one ongoing complete response, two partial remissions lasting 16 and 77 weeks and disease stabilisation (SD) in 12 patients lasting a median (range) of 17 (7-26) weeks; three of them had SD of 24, 25 and 26 weeks, respectively.Conclusion: TrasGEX was safe, well-tolerated and showed antitumour activity in 50% of evaluable patients, all with progressive disease at study entry. Infusions at an interval of 2-3 weeks should achieve clinically relevant trough levels for future studies (NCT01409343).

AB - Purpose: TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies and to define the safety, pharmacokinetics (PK) and preliminary antitumour activity of TrasGEX.Patients and methods: A total of 37 patients with advanced HER2-positive carcinomas and progressive disease received TrasGEX intravenously every 3 weeks until disease progression in doses of 12-720 mg in a three-plus-three dose escalation design, including an expansion cohort at the highest dose.Results: No dose limiting toxicity was observed, and no maximum tolerated dose was reached. Drug-related adverse events were mainly infusion-related reactions occurring during the first infusion in 51% of patients; all but two were mild-to-moderate. Compared with trastuzumab, the PK parameters were dose dependent, with a mean terminal half-life (t1/2) of 263±99 hours for the 720 mg dose. Clinical benefit in 15 out of 30 (50%) evaluable patients included one ongoing complete response, two partial remissions lasting 16 and 77 weeks and disease stabilisation (SD) in 12 patients lasting a median (range) of 17 (7-26) weeks; three of them had SD of 24, 25 and 26 weeks, respectively.Conclusion: TrasGEX was safe, well-tolerated and showed antitumour activity in 50% of evaluable patients, all with progressive disease at study entry. Infusions at an interval of 2-3 weeks should achieve clinically relevant trough levels for future studies (NCT01409343).

KW - Journal Article

U2 - 10.1136/esmoopen-2018-000381

DO - 10.1136/esmoopen-2018-000381

M3 - SCORING: Journal article

C2 - 30018811

VL - 3

SP - e000381

JO - ESMO OPEN

JF - ESMO OPEN

SN - 2059-7029

IS - 4

ER -