554P - Phase I clinical trial of OBP-301, a novel telomerase-specific oncolytic virus, in combination with radiotherapy in esophageal cancer patients

Background

OBP-301 is a novel condition-restricted, replication-competent adenovirus derived from human adenovirus type 5 that incorporates a human telomerase reverse transcriptase (hTERT) promoter. This construct causes tumor-specific viral replication and lytic death of a variety of cancer cells, and safety of OBP-301 monotherapy has been confirmed in patients with solid tumor in phase I clinical trial. We conducted phase I clinical trial to evaluate safety, tolerability and efficacy of OBP-301 in combination with radiotherapy.

Methods

This is a phase I clinical trial (NCT03213054) to evaluate safety, tolerability and efficacy of OBP-301 in combination with radiotherapy in patient with esophageal cancer who are not applicable for standard therapy. This is an open-label trial designated as standard 3 + 3 dose escalation. The dose of OBP-301 will be started from 3 x 10¹¹ virus particles (VP) in Cohort 1, and if no dose limiting toxicity (DLT) is observed, dose will be escalated to 3 x 10¹² VP. OBP-301 will be injected to primary tumor by endoscopy at Day 1, Day 18 and Day 32. From Day 4, patients receive 6 weeks radiotherapy (60 Gy total).

Results

6 patients were enrolled to the phase I clinical trial, 3 patients were treated with 3 x 10¹¹ VP and 3 x 10¹² VP of OBP-301 in the Cohort 1 and Cohort 2, respectively. All patients were male, with median age of 81.5 years. No DLT was observed, thus maximum tolerable dose (MTD) of OBP-301 was not determined, and MTD was over 10¹² VP. The adverse events related to OBP-301 were lymphocyte count decreased (83.3%, Grade2-4), pyrexia (83.3%, Grade1-2), upper respiratory tract infection (16.7%, Grade1), malaise (16.7%, Grade1), decreased appetite (16.7%, Grade2), esophagitis (16.7%, Grade2), radiation esophagitis (16.7%, Grade1), weight decreased (16.7%, Grade1). 4 of 6 patients experienced complete response (CR) in primary tumor and CR rate for primary tumor was 66.7%, and other 2 patients also experienced tumor shrinkage.

Conclusions

The combination of OBP-301 and radiotherapy was well tolerated, and able to provide definite clinical benefits in patients with esophageal cancer who are not applicable for surgery or standard chemotherapy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Oncolys Biopharma Inc.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.