TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: A phase I study in patients with solid tumors

Purpose: TNFerade is a replication deficient adenovector that expresses human tumor necrosis factor alpha under control of the radiation-inducible Egr-1 promoter. The goals of this study were to determine the safety and toxicity of TNFerade in combination with radiation therapy. Patients and Methods: TNFerade was administered by intratumoral administration, weekly for 6 weeks with concomitant radiation (30 to 70 Gy). Seven dose levels were studied (4 × 10⁷ particle units [pu] to 4 × 10¹¹ pu) in patients with solid tumors being treated with radiation. Results: Thirty-six patients were assessable for toxicity and 30 for tumor response. Most frequent TNFerade-related toxicities were fever (22%), injection site pain (19%), and chills (19%). No dose-limiting toxicities were observed. Overall, 21 of 30 patients (70%) demonstrated objective tumor response (five complete responses, nine partial responses, and seven minimal responses). In four of five patients with synchronous lesions, a differential response between lesions treated with TNFerade + radiation compared with radiation only was observed. Conclusion: This is the first human study with TNFerade and radiation. The integrated treatment was well tolerated in patients with predominantly prior treatment-refractory solid tumors. Controlled prospective clinical trials have been initiated to more fully define the therapeutic contribution of TNFerade.