A Phase I Study of Telomerase-specific Replication Competent Oncolytic Adenovirus (Telomelysin) for Various Solid Tumors

Abstract

A phase I clinical trial was conducted to determine the clinical safety of Telomelysin, a human telomerase reverse transcriptase (hTERT) promoter driven modified oncolytic adenovirus, in patients with advanced solid tumors. A single intratumoral injection (IT) of Telomelysin was administered to three cohorts of patients (1 x 10(10), 1 x 10(11), 1 x 10(12) viral particles). Safety, response and pharmacodynamics were evaluated. Sixteen patients with a variety of solid tumors were enrolled. IT of Telomelysin was well tolerated at all dose levels. Common grade 1 and 2 toxicities included injection site reactions (pain, induration) and systemic reactions (fever, chills). hTERT expression was demonstrated at biopsy in 9 of 12 patients. Viral DNA was transiently detected in plasma in 13 of 16 patients. Viral DNA was detectable in four patients in plasma or sputum at day 7 and 14 post-treatment despite below detectable levels at 24 h, suggesting viral replication. One patient had a partial response of the injected malignant lesion. Seven patients fulfilled Response Evaluation Criteria in Solid Tumors (RECIST) definition for stable disease at day 56 after treatment. Telomelysin was well tolerated. Evidence of antitumor activity was suggested.

Assessment of an altered E1B promoter on the specificity and potency of triple-regulated conditionally replicating adenoviruses: implications for the generation of ideal m-CRAs

“…Clinical trials that have examined intratumoral injections of simple CRAs, in which E1A is regulated by a single cancer-specific promoter, demonstrated sufficient safety with no reports of lethal adverse effects. 30,31 However, to date, there are no reports of clinical trials that have examined or sufficiently assessed the safety of systemic injections of simple CRAs, even though systemic injections may be more effective to treat disseminated cancer cell metastases, including metastatic osteosarcoma in lung, for which current therapies are ineffective. 1,20,32 The improved m-CRAs that were generated based on these results, including Surv.m-CRA-OCp, may facilitate clinical trials on systemic m-CRA therapy.…”

The antitumor effects of oncolytic adenovirus H101 against lung cancer

“…A variety of viruses have shown oncolytic properties including adenovirus, herpes simplex virus, Newcastle disease virus, vesicular stomatitis virus and reovirus (22). Among a variety of oncolytic viral agents, CRAds specifically aimed at killing tumor cells while sparing normal cells have been developed as new agents for cancer therapy (23,24), and demonstrated efficacy and safety in preclinical (25,26) and clinical trials (27)(28)(29). Various methods have been used to achieve a selective expression.…”

Clinical development directions in oncolytic viral therapy

“…58 A phase I study evaluating the tolerability of a single intratumoral injection of Telomelysin was recently completed. 60 Sixteen patients were entered into three dose escalation cohorts without defining a maximum tolerated dose. There were no clinically significant grade 3 or 4 treatment-related adverse events (AEs).…”