An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

The Epstein-Barr virus (EBV) may play a role in the development of various types of lymphoma, including diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma, and post-transplant lymphoproliferative disorders (PTLD). Regardless of whether EBV has been detected or not, standard treatment usually involves chemotherapy and immunotherapy. However, patients with EBV-positive lymphoma have a poorer prognosis with standard therapy than comparable patients who are EBV-negative. In most cases, the EBV infection is no longer actively present at the time the lymphoma develops; rather, it may have occurred (even unnoticed) years earlier, yet the virus remains present in the affected cells.

The aim of this Phase 2 study is to further investigate the efficacy and safety of the combination therapy of nanatinostat and valganciclovir in a selected group of patients. Nanatinostat is a selective inhibitor of histone deacetylases (HDACs) that reactivates the virus while simultaneously activating valganciclovir to combat EBV. Valganciclovir is an antiviral medication primarily used to treat immunocompromised patients with cytomegalovirus (CMV) infection. This combination is intended to specifically target and destroy cancer cells. Treatment is administered in 28-day cycles. Valganciclovir 900 mg is taken daily in tablet form. Nanatinostat 20 mg is administered as a tablet on days 1–4 of each week. All patients receive the same treatment, and the study is open-label, meaning that both the medical staff and the patient know which medications are being taken. Treatment as part of the study lasts for up to 36 months, during which the effectiveness of the therapy and the occurrence of side effects from the various medications are evaluated. The key factor is whether or when the disease progresses again during treatment. The primary endpoint of the study is the response rate to therapy after 3 years.

Patients aged 18 and older with diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), extranodal NK/T-cell lymphoma, or post-transplant lymphoproliferative disorder (PTLD) are eligible to participate in the study. The diseases must be previously treated, Epstein-Barr virus-positive (EBV+), and present as a relapse or be refractory to treatment.