Luke S McLean1, Tessa A Morris2,3, Ann Gramza4, Stephen Liu4, Saad A Khan5, A Dimitrios Colevas6, Tillman Pearce7, Danny Rischin8,9. 1. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 2. Department of Medicine, University of Otago, Dunedin, New Zealand. 3. Southern Blood and Cancer Service, Southern District Healthboard, Dunedin, New Zealand. 4. Georgetown University, Washington, D.C, United States of America. 5. University of Texas Southwestern Medical Center, Dallas, Texas, United States of America. 6. Stanford University, Stanford, California, United States of America. 7. TCellCo, San Francisco, California, United States of America. 8. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Danny.rischin@petermac.org. 9. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia. Danny.rischin@petermac.org.
Abstract
BACKGROUND: Tarloxotinib, a hypoxia-activated prodrug of an irreversible pan-ErbB tyrosine kinase inhibitor, represents a novel therapeutic which exploits the tumor-specific hypoxic environment as a mechanism for tumor-specific targeting. This study evaluated the safety and activity of tarloxotinib in recurrent or metastatic (R/M) cutaneous (CSCC) or head and neck squamous cell carcinoma (HNSCC). METHODS: This was a phase II two-stage multi-centre study for patients with R/M HNSCC or CSCC. All patients received tarloxotinib 150 mg/m2 on days 1,8,15 and 22 in a 28-day cycle. Stage 1 enrolled patients in three cohorts: p16-negative HNSCC, p16-positive oropharyngeal SCC, and CSCC. In order for a cohort to proceed to stage 2 a minimum response rate of 5% was required. RESULTS: 30 patients were enrolled: 23% were female with median age of 63.3 years. The median duration of follow-up was 20 weeks. The median progression-free survival was 2.0 months (95%CI 1.8-3.4) and median overall survival 5.7 months (95%CI 3.6-8.0). Treatment was well tolerated. The objective response rate was 3% with one patient with CSCC having a partial response. CONCLUSIONS: Hypoxia-activated prodrugs represent a novel approach to cancer treatment, however, no clinically meaningful benefit for tarloxotinib in R/M HNSCC or CSCC was identified in this study. TRIAL REGISTRATION NUMBER: NCT02449681 (May 20, 2015).
BACKGROUND: Tarloxotinib, a hypoxia-activated prodrug of an irreversible pan-ErbB tyrosine kinase inhibitor, represents a novel therapeutic which exploits the tumor-specific hypoxic environment as a mechanism for tumor-specific targeting. This study evaluated the safety and activity of tarloxotinib in recurrent or metastatic (R/M) cutaneous (CSCC) or head and neck squamous cell carcinoma (HNSCC). METHODS: This was a phase II two-stage multi-centre study for patients with R/M HNSCC or CSCC. All patients received tarloxotinib 150 mg/m2 on days 1,8,15 and 22 in a 28-day cycle. Stage 1 enrolled patients in three cohorts: p16-negative HNSCC, p16-positive oropharyngeal SCC, and CSCC. In order for a cohort to proceed to stage 2 a minimum response rate of 5% was required. RESULTS: 30 patients were enrolled: 23% were female with median age of 63.3 years. The median duration of follow-up was 20 weeks. The median progression-free survival was 2.0 months (95%CI 1.8-3.4) and median overall survival 5.7 months (95%CI 3.6-8.0). Treatment was well tolerated. The objective response rate was 3% with one patient with CSCC having a partial response. CONCLUSIONS: Hypoxia-activated prodrugs represent a novel approach to cancer treatment, however, no clinically meaningful benefit for tarloxotinib in R/M HNSCC or CSCC was identified in this study. TRIAL REGISTRATION NUMBER: NCT02449681 (May 20, 2015).
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