Study for Treatment of Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin

A Phase 2 Study of Tarloxotinib (TH-4000) in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck or Skin

This phase 2 study is designed to evaluate the safety and activity of TH-4000, a hypoxia-activated prodrug in participants with recurrent or metastatic squamous cell carcinoma of the head and neck or skin.

An open label, multi-center Phase 2 study in which the pharmacokinetics, safety, tolerability and efficacy of TH-4000 will be assessed in participants with recurrent or metastatic squamous cell carcinoma of the head and neck or skin.

Hypoxia PET scans will be obtained in select centers to analyze potential predictors of tumor response.

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Confirmed squamous cell carcinoma (SCC) of the head and neck (oropharynx, oral cavity, hypopharynx, or larynx) or skin
• For patients with oropharyngeal cancer, p16 status is known or can be determined
• Measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
• Acceptable laboratory results as indicated by protocol
• Acceptable cardiac function as indicated by protocol

Exclusion Criteria:

• Received prior epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) therapy for recurrent or metastatic Squamous Cell Carcinoma (e.g., oral EGFR TKIs such as erlotinib, gefitinib, or afatinib)
• Family history of long corrected QT interval (QTc) syndrome
• Receiving medication that prolongs QT interval ,with a risk of causing Torsades de Pointes (TdP), unless ECG meets inclusion criteria while on a stable dose of the medication
• Family history of long QTc syndrome
• Symptomatic central nervous system (CNS) lesions, or CNS lesions that require therapy
• Radiation therapy within 2 weeks prior to the first dose of study medication
• Major surgery within 4 weeks or minor surgery within 2 weeks prior to the first dose of study medication
• Concurrent active malignancy requiring systemic treatment
• Any other serious uncontrolled medical disorders or psychological conditions that may interfere with study conduct including but not limited to: clinically significant active infection
• Pregnant or breast-feeding