Efficacy and Safety of Glembatumumab Vedotin in Patients With Advanced or Metastatic Squamous Cell Carcinoma of the Lung (PrECOG 0504)

• Type of Material: Article
• Authors: Saad A Khan, Harold C. Simmons Comprehensive Cancer Center, Dallas; Zhuoxin Sun, Dana-Farber Cancer Institute; Suzanne Dahlberg, Dana-Farber Cancer Institute; Jyoti Malhotra, Rutgers Cancer Institute of New Jersey; Roger Keresztes, Stony Brook Medicine; Chukwuemeka Ikpeazu, University of Miami Leonard M. Miller School of Medicine; Patrick Ma, Pennsylvania State University; Suresh Ramalingam, Emory University; Rathi Pillai, Emory University
• Language: English
• Date: 2021-05-01
• Publisher: Elsevier Inc
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jtocrr.2021.100166
• Title of Journal or Parent Work: JTO Clinical and Research Reports
• Volume: 2
• Issue: 5
• Start Page: 100166
• End Page: 100166
• Keywords: DC-HIL; Squamous cell lung cancer; Targeted therapy; gpNMB
• Research Categories: Health Sciences, Oncology

Abstract

Introduction: Glycoprotein NMB is a transmembrane protein linked with poor prognosis and is expressed in most squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting glycoprotein NMB, administered intravenously every 3 weeks in this phase 1 study to determine the safety, tolerability, and maximum tolerated dose in patients who had progressed on any number of previous therapies. Results: A total of 13 patients were enrolled; adverse events (of any grade) including dyspnea, neutropenia, respiratory failure, anemia, increased aspartate transaminase/alanine transaminase, diarrhea, and hypophosphatemia were seen in 15% of patients. Grade 5 events included two cases of respiratory failure, either completely or partially attributed to cancer progression. The only other grade 5 event was “disease progression.” The most common adverse events (23%) were decreased appetite, fatigue, rash, and weight loss. The median overall and progression-free survivals were 5.7 months (90% confidence interval: 2.5–16.8) and 2.5 months (90% confidence interval: 1.6–5.8) respectively. Conclusions: Glembatumumab vedotin exhibited no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anticancer activity was observed with a recommendation for a phase 2 dose of 1.9 mg/kg. This portion of the study was not undertaken owing to the company's decision to discontinue drug development.