Authors: Almhanna K, Wright D, Mercade TM, Van Laethem JL, Gracian AC,Guillen-Ponce C, Faris J, Lopez CM, Hubner RA, Bendell J, Bols A, Feliu J, Starling N, Enzinger P, Mahalingham D, Messersmith W, Yang H, Fasanmade A, Danaee H, Kalebic T.

Published in: Invest New Drugs. 2017 May 19. doi: 10.1007/s10637-017-0473-9. [Epub ahead of print]

Keywords: Antibodies, immunoconjugates, Antibody immunotherapy, Antibody–drug conjugate, Guanylyl cyclase C, Phase II trials, Pancreatic cancers, Pancreas, TAK-264, MLN0264, indusatumab vedotin.

In an article published in the May 19, 2017 edition of Investigational New Drugs | The Journal of New Anticancer Agents (ISSN: 0167-6997 | 1573-0646, a journal published by Springer Nature Khaldoun Almhanna from the Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL, David Wright (Florida Cancer Specialists, Tampa, FL), Teresa Macarulla Mercade (Vall d’Hebron University Hospital, Barcelona, Spain), et all, evaluated, in a phase II open-label, multicenter study, the efficacy, safety, and tolerability of TAK-264, also known as MLN0264 and indusatumab vedotin (being developped by Millenium/Takeda), in previously treated patients with advanced or metastatic pancreatic adenocarcinoma expressing guanylyl cyclase C (GCC).

Advertisement #3 

TAK-264 is a monoclonal antibody (indusatumab) that targets the enzyme guanylate cyclase 2C which is present in some cancers, linked to an average of three to four molecules of the chemotherapeutic agent monomethyl auristatin E (MMAE).

In this study, patients with advanced or metastatic pancreatic adenocarcinoma expressing GCC (H-score ≥ 10) received TAK-264 1.8 mg/kg on day 1 of a 21-day cycle as a 30-min intravenous infusion for up to 1 year or until disease progression or unacceptable toxicity.

Study Objectives
The primary objective was overall response rate (ORR [complete response + partial response (PR)]).

Secondary objectives included evaluations of the safety and pharmacokinetic profile of TAK-264 (NCT02202785).

A total of 43 patients were enrolled and treated with 1.8 mg/kg TAK-264: 11, 15, and 17 patients with low, intermediate, and high GCC expression, respectively. Median number of treatment cycles received was two (range 1-10). The ORR was 3%, including one patient with intermediate GCC expression who achieved a PR. All patients experienced ≥1 adverse events (AE). The majority of patients experienced grade 1/2 Adverse Events included AEs affecting the gastrointestinal tract. Fifteen (35%) patients experienced ≥grade 3 drug-related AEs; five (12%) patients had a serious AE. The most common (≥10% of patients) all-grade drug-related AEs were nausea (33%), fatigue (28%), neutropenia (23%), decreased appetite (23%), vomiting (16%), asthenia (16%), and alopecia (14%).

The researchers concluded that TAK-264 (MLN0264) demonstrated a manageable safety profile. However, the low efficacy of TAK-264 observed in this study did not support further clinical investigation.

Study: Takeda Oncology, Millenium

Last Editorial Review: May 19, 2017


Advertisement #4