FDA Gives OK for Viracta’s Phase Ib/II Trial of Oral Combo in Epstein-Barr Virus Tumors
The U.S. Food and Drug Administration (FDA) has cleared an Investigational New Drug (IND) application for a Phase Ib/II trial of Viracta Therapeutics’ all-oral combination regimen in advanced Epstein-Barr Virus-Positive (EBV+) solid tumors. The study will also investigate the oral combination with PD-1 inhibitor pembrolizumab in EBV+ metastatic nasopharyngeal carcinoma (RM-NPC).
Researchers of the Phase Ib/II trial will place focus on the company’s orally available histone deacetylase (HDAC) inhibitor nanatinostat (VRx-3996). This agent, which was designed to be selective for certain isoforms of Class I HDACs, is essential for inducing viral genes epigenetically silenced in EBV-associated cancers or tumors. The study will specifically investigate nanatinostat combined with valganciclovir, a combination regimen currently studied in several subtypes of relapsed/refractory EBV+ lymphoma in two Phase II trials.
In the Phase Ib dose escalation part of Viracta’s newly cleared study, researchers will examine the combo’s safety and pharmacokinetics and identify the recommended Phase II dose of nanatinostat and valganciclovir for expansion in EBV+ solid tumors. Following this portion of the study, researchers will test the safety, preliminary efficacy and potential pharmacodynamic markers of the combination regimen alone and with pembrolizumab in patients with EBV+ RM-NPC patients in the Phase II portion of the trial.
Viracta hopes to start the trial in the second half of this year. According to Lisa Rojkjaer, M.D., chief medical officer of the company, the IND clearance represents a “crucial milestone” for Viracta, particularly in regard to its focus on EBV-associated malignancies. “EBV is the primary etiologic agent for NPC, one of the most commonly reported head and neck cancers worldwide,” said Dr. Rojkjaer, in a statement.
The prognosis of patients with RM-NPC is generally poor, as there are no currently available standard therapies for second or later lines of treatment. Patients with RM-NPC tend to have an overall survival expectancy of less than 20 months.
Patients with NPC often demonstrate high expression of PD-L1, and the use of PD-1 inhibitors for RM-NPC tend to demonstrate preliminary response rates of 20% to 30%. “Given the encouraging activity seen in our Phase Ib/II trial of nanatinostat and valganciclovir in patients with EBV+ recurrent lymphomas, we now turn to evaluating this combination in patients with other EBV+ malignancies and explore potential synergies with checkpoint inhibition.”
Viracta’s President and Chief Executive Officer, Ivor Royston, M.D., said the expansion of the company’s “solid tumor program is an important component of our clinical and corporate strategy, and one that could significantly expand our addressable patient population and unlock significant value to shareholders.”
News of the IND clearance for the Phase Ib/II trial follow the company’s announcement earlier this summer of the initiation of a global pivotal trial for relapsed/refractory EBV+ lymphoma. The open-label, Phase II basket trial, dubbed NAVAL-1, is evaluating the same nanatinostat and valganciclovir combination. Viracta hopes the study will support several new drug application filings across this indication.
“We are seeing enthusiasm for NAVAL-1 and our therapeutic approach from physicians, both in the United States and internationally, as this is an area of significant unmet medical need,” said Dr. Rojkjaer, in a statement about the trial.
The NAVAL-1 trial is working to enroll up to 140 patients across North America, Europe and Asia-Pacific. Primary and key secondary endpoints include objective response rates and duration of response, survival outcomes and safety, respectively.