Nanatinostat Plus Valganciclovir in Advanced EBV+ Solid Tumors and in Combination With Pembrolizumab in EBV+ RM-NPC

Open-Label Multicenter Phase 1b/2 Study of Nanatinostat + Valganciclovir in Patients With Advanced Epstein-Barr Virus-Positive Solid Tumors and in Combination With Pembrolizumab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

This study will evaluate the safety and efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive solid tumors and in combination with pembrolizumab in patients with recurrent/metastatic nasopharyngeal carcinoma

This is an open-label, multicenter Phase 1b/2 study evaluating nanatinostat in combination with valganciclovir alone and in combination with pembrolizumab. Nanatinostat is a selective class I HDAC inhibitor which induces EBV early lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form.

The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) in patients with EBV+ RM-NPC followed by a Project Optimus | FDA (https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus) cohort to confirm the RP2D. Up to 60 patients with EBV+ RM-NPC will be randomized 1:1 to receive nanatinostat in combination with valganciclovir at the confirmed RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers in the Phase 2 dose expansion part of the study. Additionally, patients with other EBV+ solid tumors will be enrolled to receive nanatinostat in combination with valganciclovir at the RP2D in a Phase 1b cohort.

The study was prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.

Key Inclusion Criteria:

• Recurrent or metastatic EBV+ nasopharyngeal carcinoma (RM-NPC) for whom no potentially curative options are available, who have received at least 1 prior line of platinum-based chemotherapy and no more than 3 prior lines of therapy for RM-NPC.
• Phase 1b exploratory proof-of-concept cohort only: Advanced/metastatic EBV+ non-NPC solid tumors with no available curative therapies.
• Measurable disease per RECIST v1.1
• ECOG performance status 0 or 1
• Adequate bone marrow and liver function

Key Exclusion Criteria:

• Anti-tumor treatment with cytotoxic drugs, biologic therapy, immunotherapy, or other investigational drugs within 4 weeks or >5 half-lives, whichever is shorter
• Active CNS disease
• 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
• Active autoimmune disease that has required systemic therapy with modifying agents, corticosteroids, or immunosuppressive agents
• Positive hepatitis B or hepatitis C