NRG-GI007: Phase I study of OBP-301, an oncolytic virus, and definitive chemoradiation in locally advanced esophageal cancer.

Abstract

Definitive chemoradiation (CRT) is standard for patients with medically inoperable esophageal cancer. OBP-301 is a modified adenovirus that adds a human telomerase reverse transcriptase gene promoter, replicating only in tumor cells to cause lysis. In this phase 1 study, OBP-301 was added to carboplatin/paclitaxel and RT (50.4 Gy). Patients received intra-tumoral OBP-301 via endoscopy 3 days prior to and then at Days 12 and 26 of RT. The primary endpoint was protocol-defined dose-limiting toxicity (DLT). Secondary endpoints included clinical complete response (cCR) rate, number alive and alive without progression at 1 year. From June 2020 to July 2024, 15 evaluable patients were enrolled. Fourteen patients (93%) received all planned OBP-301 injections and 50.4 Gy RT. No DLTs were observed. The most common treatment-related grade 3/4 toxicities were neutropenia (40%) and lymphopenia (33%). Two patients died prior to restaging: 1 patient developed grade 5 respiratory failure 6 weeks after CRT (suspected RT pneumonitis), while a second patient had unrecognized airway involvement at baseline, which led to a tracheoesophageal fistula during Week 3 of CRT. The cCR rate for patients undergoing restaging (n=13) was 100% (95% CI: 77, 100), and 87% (95% CI: 62, 96) for all 15 patients. At 1 year, 9 (60%) out of 15 patients are still alive and 8 (53%) are alive without progression. OBP-301 administration before and during CRT is feasible and safe, resulting in a very promising cCR rate. A randomized study is being planned to further evaluate safety and efficacy.