An Open-Label Phase 2 Trial of Nanatinostat Plus Valganciclovir in Patients With EBV+ Relapsed/Refractory Lymphomas

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:

1. Diffuse large B-cell lymphoma (DLBCL)
2. Extranodal natural killer/T-cell lymphoma (ENKTL)
3. Peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS)
4. Hodgkin lymphoma (HL)
5. Post-transplant lymphoproliferative disorders (PTLD)
6. Human immunodeficiency virus (HIV)-associated lymphomas (HIV-L)
7. EBV+ lymphomas other than the above

The study was terminated prematurely and did not reach its target enrollment.

Key Inclusion Criteria:

• 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).