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

Saad A Khan; Zhuoxin Sun; Suzanne Dahlberg; Jyoti Malhotra; Roger Keresztes; Chukwuemeka Ikpeazu; Patrick Ma; Suresh S Ramalingam; Rathi Pillai

doi:10.1016/j.jtocrr.2021.100166

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

JTO Clin Res Rep. 2021 Mar 24;2(5):100166. doi: 10.1016/j.jtocrr.2021.100166. eCollection 2021 May.

Authors

Saad A Khan^{1

2}, Zhuoxin Sun³, Suzanne Dahlberg^{3

4}, Jyoti Malhotra⁵, Roger Keresztes⁶, Chukwuemeka Ikpeazu⁷, Patrick Ma⁸, Suresh S Ramalingam⁹, Rathi Pillai⁹

Affiliations

¹ Harold C. Simmons Comprehensive Cancer Center, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas.
² Current Affiliation: Cancer Institute, Stanford Medicine, Stanford University, Stanford, California.
³ Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute, Boston, Massachusetts.
⁴ Current Affiliation: Department of Pediatrics, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts.
⁵ Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, New Jersey.
⁶ Stony Brook Cancer Center, Stony Brook University, Stony Brook, New York.
⁷ Division of Medical Oncology, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, Florida.
⁸ Department of Medicine, Penn State University, State College, Pennsylvania.
⁹ Department of Hematology/Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia.

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.

Keywords: DC-HIL; Squamous cell lung cancer; Targeted therapy; gpNMB.