A phase II study of tarloxotinib (a hypoxia activated prodrug of a pan-erb tyrosine kinase inhibitor) in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or skin

McLean, LS; Morris, TA; Gramza, A; Liu, S; Khan, SA; Colevas, AD; Pearce, T; Rischin, D

Author(s): McLean, LS; Morris, TA; Gramza, A; Liu, S; Khan, SA; Colevas, AD; Pearce, T; Rischin, D;
Details: Publication Year 2022-08,Volume 40,Issue #4,Page 782-788
Journal Title: Investigational New Drugs
Publication Type: Research article
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).
Keywords: Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Carcinoma, Squamous Cell/pathology; Female; *Head and Neck Neoplasms/drug therapy; Humans; Hypoxia/drug therapy; Male; Middle Aged; Neoplasm Recurrence, Local/drug therapy/pathology; *Prodrugs/adverse effects; Protein Kinase Inhibitors/adverse effects; Squamous Cell Carcinoma of Head and Neck/drug therapy; Cutaneous squamous cell carcinoma; Egfr; Head and neck squamous cell carcinoma; Hypoxia-activated prodrugs; Phase II
Department(s): Medical Oncology
PubMed ID: 35435625
Publisher's Version: https://doi.org/10.1007/s10637-022-01230-w
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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