An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas
A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas
Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas:
EBV+ diffuse large B-cell lymphoma (DLBCL, NOS) Peripheral T-cell lymphoma (PTCL), including PTCL-NOS and AITL Post-transplant lymphoproliferative disorder (PTLD) EBV+ lymphoproliferative disorders other than the above, including Extranodal NK/T-cell lymphoma (ENKTL)
EBV+ DLBCL, NOS and PTCL, NOS, and AITL: Relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent. For EBV+ PTLD patients: Relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-CD20 immunotherapy. For patients with EBV+ PTLD only, age 12 years and older and weighing greater than 40 kg (Adolescent, Adult, Older Adult) are allowed For other EBV+ relapsed/refractory lymphoma: Following at least 1 course of an anit-CD20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated) No available therapies in the opinion of the Investigator Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy Measurable disease per Cheson 2007 ECOG performance status 0, 1, 2 Adequate bone marrow function
Key Exclusion Criteria:
Presence or history of CNS involvement by lymphoma Systemic anticancer therapy or CAR-T within 21 days Antibody (anticancer) agents within 28 days Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant Less than 90 days from prior allogeneic transplant. Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1 Inability to take oral medication, malabsorption syndrome or any other gastrointestinal condition (nausea, diarrhea, vomiting) that may impact the absorption of nanatinostat and valganciclovir. Active infection requiring systemic therapy (excluding viral upper respiratory tract infections).
