title: A phase 1 clinical trial of ASG-5ME, a novel drug-antibody conjugate targeting SLC44A4, in patients with advanced pancreatic and gastric cancers.
abstract: Purpose ASG-5ME is an antibody-drug conjugate (ADC) targeting SLC44A4, a novel cell surface target expressed on most pancreatic and gastric cancers. This first-in-human study of ASG-5ME evaluated safety, pharmacokinetics, and preliminary activity of ASG-5ME in advanced pancreatic and gastric cancer patients. Experimental Design This phase 1, dose-escalation, multicenter study determined the maximum tolerated dose (MTD) and assessed safety and antitumor activity. The dose-escalation portion enrolled metastatic pancreatic adenocarcinoma patients; gastric adenocarcinoma patients were included in the dose-expansion portion. Patients received ASG-5ME intravenously on Days 1, 8, and 15 of 28-day cycles. Results Thirty-five pancreatic cancer patients (median age 63 years; performance status 0 [40 %] or 1 [60 %]) were treated at doses of 0.3 to 1.5 mg/kg (median duration 8.1 weeks). The MTD was exceeded at 1.5 mg/kg (n = 7) with 1 dose-limiting toxicity (DLT) of Grade 4 gastrointestinal hemorrhage. Four patients experienced non-DLT Grade 3 or 4 neutropenia. Fifteen gastric cancer patients (median age 59 years; performance status 0 [33 %] or 1 [67 %]) were treated at the identified MTD of 1.2 mg/kg (median duration 8.7 weeks). Common drug-related adverse events included fatigue (29 %), nausea (23 %), and vomiting (23 %) for pancreatic cancer patients and fatigue (33 %) and decreased appetite (33 %) for gastric cancer patients. Best clinical response was 1 partial response in each cohort. Disease-control rates of 33 % (pancreatic) and 47 % (gastric) were observed at the MTD. All patient biopsies (23 pancreatic, 15 gastric) expressed the SLC44A4 antigen. Conclusions ASG-5ME treatment was generally well tolerated with limited evidence of antitumor activity.
authors.affiliation: Seattle Cancer Care Alliance, University of Washington, 825 Eastlake Ave E, Seattle, WA, 98109, USA. acoveler@u.washington.edu.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Coveler
authors.affiliation: Comprehensive Cancer Center, University of California at San Francisco, San Francisco, CA, USA.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
authors.affiliation: University of Chicago, Chicago, IL, USA.
authors.forename: Daniel V T
authors.initials: DV
authors.lastname: Catenacci
authors.affiliation: TGen Clinical Research Service at Scottsdale Healthcare, Scottsdale, AZ, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Von Hoff
authors.affiliation: Texas Oncology, Baylor Sammons Cancer Center, Dallas, TX, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Becerra
authors.affiliation: Seattle Genetics, Inc., Bothell, WA, USA.
authors.forename: Nancy C
authors.initials: NC
authors.lastname: Whiting
authors.affiliation: Seattle Genetics, Inc., Bothell, WA, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Wolpin
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D026901:Membrane Transport Proteins / Q000378:metabolism; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: C583373:ASG-5ME; D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins; D009842:Oligopeptides; C583905:SLC44A4 protein, human
keywords: ADC; ASG-5ME; Antibody-drug conjugate; Solid tumor