Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/30614
Title: A phase 1 safety and bioimaging trial of antibody DS-8895a against EphA2 in patients with advanced or metastatic EphA2 positive cancers.
Austin Authors: Gan, Hui K ;Parakh, Sagun ;Lee, Fook-Thean;Tebbutt, Niall C ;Ameratunga, Malaka;Lee, Sze Ting ;O'Keefe, Graeme J;Gong, Sylvia J;Vanrenen, Christine;Caine, Jaren;Giovannetti, Mara;Murone, Carmel ;Scott, Fiona E;Guo, Nancy;Burvenich, Ingrid J G;Paine, Cameron;Macri, Mary J;Kotsuma, Masakatsu;Senaldi, Giorgio;Venhaus, Ralph;Scott, Andrew M 
Affiliation: Olivia Newton-John Cancer Research Institute
School of Cancer Medicine, La Trobe University, Melbourne, Australia..
Medical Oncology
School of Cancer Medicine, La Trobe University, Melbourne, Australia..
Molecular Imaging and Therapy
Faculty of Medicine, University of Melbourne, Melbourne, Australia..
Ludwig Cancer Research, New York, NY, USA..
Daiichi Sankyo, Inc, Basking Ridge, NJ, USA..
Issue Date: Aug-2022
Date: 2022
Publication information: Investigational New Drugs 2022; 40(4): 747-755
Abstract: Ephrin type-A 2 (EphA2) is a transmembrane receptor expressed in epithelial cancers. We report on a phase I dose escalation and biodistribution study of DS-8895a, an anti-EphA2 antibody, in patients with advanced EphA2 positive cancers. DS-8895a was administered at 1, 3, 10 or 20 mg/kg every 2 weeks to determine safety, pharmacokinetics and anti-tumor efficacy. All patients underwent 89Zr trace-labelled infusion of DS-8895a (89Zr-DS-8995a) positron emission tomography imaging to determine the biodistribution of DS-8895a, and correlate findings with EphA2 expression, receptor saturation and response. Nine patients were enrolled on study. Of patients enrolled, seven patients received at least one infusion of DS-8895a: four patients received 1 mg/kg dose (Cohort 1) and three patients received 3 mg/kg dose (Cohort 2). Median age was 67.0 years (range 52-81), majority male (71%), and median number of prior systemic therapies was three (range 0-8). The primary cancer diagnosis was colorectal cancer (two patients) and one patient each had gastric, head and neck, high-grade serous adenocarcinoma, lung, and pancreatic cancers. No dose-limiting toxicities or treatment-related adverse events reported. The best response for the patients in Cohort 1 was stable disease and in Cohort 2 was progressive disease. 89Zr-DS-8895a demonstrated no normal tissue uptake and specific low-grade uptake in most tumours. DS-8895a had limited therapeutic efficacy at doses evaluated and 89Zr-DS-8895a demonstrated low tumour uptake. The biodistribution data from this study were key in halting further development of DS-8895a, highlighting the importance of biodistribution studies in drug development. (Trial registration: ClinicalTrials.gov Identifier NCT02252211).
URI: https://ahro.austin.org.au/austinjspui/handle/1/30614
DOI: 10.1007/s10637-022-01237-3
ORCID: http://orcid.org/0000-0001-7319-8546
https://orcid.org/0000-0003-3891-2489
https://orcid.org/0000-0001-6755-3951
https://orcid.org/0000-0003-2613-5168
https://orcid.org/0000-0002-7171-6781
https://orcid.org/0000-0001-8641-456X
https://orcid.org/0000-0002-8538-6170
https://orcid.org/0000-0003-2426-1638
https://orcid.org/0000-0001-8384-2403
https://orcid.org/0000-0002-6656-295X
Journal: Investigational new drugs
PubMed URL: 35404015
PubMed URL: https://pubmed.ncbi.nlm.nih.gov/35404015/
Type: Journal Article
Subjects: 89Zr-DS-8895a
DS-8895a
EphA2
Imaging
Appears in Collections:Journal articles

Show full item record

Page view(s)

42
checked on Apr 19, 2024

Google ScholarTM

Check


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.