Nanatinostat With Valganciclovir Produces Positive Topline Data in EBV+ PTCL

Hung Chang, MD

Viracta Therapeutics has announced positive topline data from stage 1 of the phase 2 NAVAL-1 trial (NCT05011058) evaluating the oral HDAC inhibitor nanatinostat with or without the antiviral agent valganciclovir in patients with relapsed/refractory Epstein-Barr virus (EBV)–positive peripheral T-cell lymphoma (PTCL).¹

Patients treated with nanatinostat in combination with valganciclovir (Nana-val; n = 10) achieved clinically meaningful antitumor responses, including an overall response rate (ORR) of 50% and a complete response (CR) rate of 20% in the intent-to-treat (ITT) population. These rates were 71% and 29%, respectively, in the efficacy-evaluable population (n = 7). The combination was also associated with a generally manageable safety profile.

Findings from NAVAL-1 were presented at the 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan.

“[Nanatinostat with valganciclovir] demonstrated an impressive clinical response [rate] in patients with relapsed or refractory EBV-positive PTCL with a generally manageable safety profile, including 1 patient who was able to proceed to allogeneic stem-cell transplant and remains in response for over 8 months to date,” Hung Chang, MD, a professor of hematology at the Linkou Chang Gung Memorial Hospital, the Chang Gung University College of Medicine, in Taoyuan, Taiwan, and principal investigator of the NAVAL-1 trial, stated in a news release. “The substantially greater clinical efficacy of [nanatinostat with valganciclovir] relative to nanatinostat monotherapy suggests that both agents in the combination regimen are contributing to its antitumor activity as predicted by their mechanisms of action. [Nanatinostat with valganciclovir] is emerging as a promising, generally well-tolerated, convenient all-oral treatment for patients with relapsed/refractory EBV-positive PTCL.”

Stage 1 of NAVAL-1 enrolled 20 patients with primarily stage III to IV EBV-positive PTCL who had received at least 1 and a median of 2 prior systemic therapies for PTCL. Patients were randomly assigned 1:1 to receive oral nanatinostat at 20 mg once daily for 4 days a week as monotherapy or in combination with oral valganciclovir at 900 mg once daily for 7 days a week. Patients who did not respond to nanatinostat monotherapy after receiving the agent for 6 weeks were permitted to cross over to treatment with the combination.

At a data cutoff of February 7, 2024, in the nanatinostat monotherapy arm (n = 10), the respective ORR and CR rate was 10% and 0% in the ITT population, and the efficacy-evaluable population (n = 8) achieved a 13% ORR. Five patients from the monotherapy arm crossed over to receive the combination. Two of these patients remained on treatment with stable disease as of the data cutoff.

The most common treatment-related adverse effects (AEs) in both arms were anemia, thrombocytopenia, fatigue, nausea, decreased appetite, weight loss, and diarrhea. These AEs were mostly mild to moderate in severity and were generally reversible or manageable.

“Patients with relapsed or refractory EBV-positive PTCL have a very poor prognosis, worse than those with EBV-negative disease, yet there are presently no EBV-targeted treatment options available,” Darrel P. Cohen, MD, PhD, chief medical officer of Viracta, added in the news release. “We are encouraged by the stage 1 data from patients with relapsed or refractory EBV-positive PTCL in the pivotal phase 2 NAVAL-1 trial that further validates [nanatinostat with valganciclovir’s] differentiated ‘Kick and Kill’ mechanism of action. Building on these promising clinical outcomes emerging from the NAVAL-1 trial, which are consistent with those from our preceding phase 1b/2 study, we will continue to advance [nanatinostat with valganciclovir] in this lead indication through regulatory approval as quickly as possible. We look forward to engaging with the FDA on a potential accelerated approval pathway midyear and sharing topline results from stage 2 together with additional data from stage 1 in the third quarter of 2024.”

Stage 2 of NAVAL-1 will enroll 11 patients with lymphoma subtypes expanded from those included in stage 1.² This trial includes the potential to further expand lymphoma subtypes after stage 2 in indications where the combination exhibits promising antitumor activity, which may further support regulatory action.

References

1. Viracta Therapeutics announces positive topline nana-val results from stage.1 of the NAVAL-1 trial in patients with relapsed or refractory Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma. News release. Viracta Therapeutics, Inc. April 15, 2024. Accessed April 15, 2024. https://viracta.investorroom.com/2024-04-15-Viracta-Therapeutics-Announces-Positive-Topline-Nana-val-Results-from-Stage-1-of-the-NAVAL-1-Trial-in-Patients-with-Relapsed-or-Refractory-Epstein-Barr-Virus-Positive-EBV-Peripheral-T-Cell-Lymphoma
2. Chang H, Hsiao H, Chen T, et al. A global phase 2 trial of nanatinostat in combination with valganciclovir in patients with EBV-positive (EBV+) relapsed/refractory peripheral T-cell lymphomas (NAVAL-1). Presented at: 2024 Joint Annual Congress of Taiwan Society of Blood and Marrow Transplantation and The Hematology Society of Taiwan; April 13-14, 2024. Kaohsiung, Taiwan.