Reference Detail

Ref Type

Journal Article

PMID

(30018811)

Authors

Fiedler W, Stoeger H, Perotti A, Gastl G, Weidmann J, Dietrich B, Baumeister H, Danielczyk A, Goletz S, Salzberg M, De Dosso S

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
ESMO open	3	4	2018	e000381	ESMO Open

URL

Abstract Text

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.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.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.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).

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials
Timigutuzumab	Timigutuzumab	0	0

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description
Timigutuzumab		TrasGEX	HER2 (ERBB2) Antibody 72	Timigutuzumab is a second-generation ERBB2 (HER2) antibody derived from trastuzumab, which has potential antitumor activity and enhances antibody-dependent cellular cytotoxicity (PMID: 30018811).

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References