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

Viracta Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Nasopharyngeal Carcinoma; EBV-Related Sarcoma; EBV Related Carcinoma; EBV-Related Leiomyosarcoma; EBV-Related Gastric Carcinoma

Treatments: Drug: Valganciclovir; Drug: Pembrolizumab; Drug: Nanatinostat

Study type: Interventional

Funder types: Industry

Identifiers

NCT05166577

VT3996-301

Details and patient eligibility

About

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

Full description

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.

Enrollment: 130 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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130 participants in 2 patient groups

Nanatinostat in combination with valganciclovir

Experimental group

Treatment:

Drug: Nanatinostat

Drug: Nanatinostat

Drug: Valganciclovir

Nanatinostat in combination with valganciclovir and pembrolizumab

Experimental group

Treatment:

Drug: Nanatinostat

Drug: Nanatinostat

Drug: Pembrolizumab

Drug: Valganciclovir