Endoscopic intratumoral injection of OBP-301 (telomelysin) with radiotherapy in esophageal cancer patients unfit for standard treatments.

Abstract

130 Background: OBP-301 (telomelysin) is an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase (hTERT) promoter to regulate viral replication. OBP-301 causes selective replication and lysis of a variety of cancer cells, and also inhibits the repair of radiation-induced DNA double-strand breaks, leading to radiosensitization. We aimed to assess intratumoral injection of OBP-301 with radiotherapy in esophageal cancer patients unfit for standard treatments. Methods: An open-label, phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed esophageal cancer patients who deemed unfit to receive surgery or chemotherapy. Study treatment consisted of intratumoral OBP-301 injections on days 1, 18, and 32 of treatment. Radiation therapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Virus administration was performed by intratumoral needle injection of the primary tumor through a flexible endoscope. The primary and secondary end points were incidence of dose-limiting toxicities and objective response rate. Results: Of 13 patients, seven, three, and three patients were treated in the cohorts with 1010, 1011, and 1012 virus particles of OBP-301, respectively. The patients comprised 10 males and 3 females, with median age of 79.7 years (range, 53 to 92 years). Common grade 1 and 2 toxicities included fever, esophagitis, pneumonitis, anorexia, constipation, and gastroesophageal reflux. All patients developed a transient, self-limited lymphopenia. Eight patients had local complete response (CR); all of them exhibited pathologically no viable malignant cells in biopsy specimens, and three had partial response. The objective response rate was 84.6%. The clinical CR rate was 80.0% in stage I and 66.7% in stage II/III, respectively. Histopathologic examination in post-treatment specimens showed massive infiltration of CD8+ cells in three partially responded tumors. Conclusions: Multiple courses of endoscopic OBP-301 injection with radiotherapy were feasible and provided definite clinical benefits in patients with esophageal cancer. Clinical trial information: 000010158.