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: Andrew L Coveler, Andrew H Ko, Daniel V T Catenacci, Daniel Von Hoff, Carlos Becerra, Nancy C Whiting, Jing Yang, Brian Wolpin
• Journal: Investigational new drugs (Invest New Drugs) Vol. 34 Issue 3 Pg. 319-28 (06 2016) ISSN: 1573-0646 [Electronic] United States
• PMID: 26994014 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

• ASG-5ME
• Antibodies, Monoclonal
• Antineoplastic Agents
• Membrane Transport Proteins
• Oligopeptides
• SLC44A4 protein, human

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics)
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics)
• Dose-Response Relationship, Drug
• Female
• Humans
• Male
• Maximum Tolerated Dose
• Membrane Transport Proteins (metabolism)
• Middle Aged
• Oligopeptides (administration & dosage, adverse effects, pharmacokinetics)
• Pancreatic Neoplasms (drug therapy, pathology)
• Stomach Neoplasms (drug therapy, pathology)
• Treatment Outcome