Brief Report: Efficacy and safety of glembatumumab vedotin in patients with advanced or metastatic squamous cell carcinoma of the lung (PrECOG 0504)

Focused Abstract: Introduction Glycoprotein NMB (gpNMB) is a transmembrane protein linked with poor prognosis and is expressed in the majority of squamous lung cancer. Glembatumumab vedotin is an antibody-drug conjugate targeting gpNMB, administered intravenously every 3 weeks in this phase I study to determine safety, tolerability and maximum tolerated dose in patients who had progressed on any number of prior therapies. Results 13 patients were enrolled; Adverse events (AE) of any grade were dyspnea, neutropenia, respiratory failure, anemia, >AST/ALT, diarrhea, hypophosphatemia seen in 15% of patients. Grade 5 events included 2 "respiratory failure"; completely or partially attributed to cancer progression. The only other grade 5 event was "disease progression". The most common AE's (23%) were decreased appetite, fatigue, rash and weight loss. Median overall and progression free survival were 5.7 months (90% CI: 2.5-16.8) and 2.5 months (90% CI: 1.6-5.8) respectively. Conclusions Glembatumumab vedotin showed no serious or unexpected toxicity in this heavily pretreated population, except those caused by disease progression. Modest anti-cancer activity was observed with a recommend for Phase 2 dose of 1.9mg/kg. This portion of the study was not undertaken due to the company's decision to discontinue drug development.