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

Phase 1TerminatedNCT05166577

Viracta Therapeutics, Inc.26 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Nasopharyngeal Carcinoma EBV-Related Gastric Carcinoma EBV-Related Leiomyosarcoma EBV Related Carcinoma EBV-Related Sarcoma

Interventions

NanatinostatDRUG

Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, then Phase 2: Nanatinostat at the confirmed recommended Phase 2 dose

ValganciclovirDRUG

Phase 1b: Valganciclovir starting at 900 mg orally daily, then Phase 2: Valganciclovir at the confirmed recommended Phase 2 dose

PembrolizumabDRUG

Phase 2: Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Stanford Cancer Center

Stanford, California, United States

University of Colorado Hospital

Aurora, Colorado, United States

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Outcomes

Primary Outcomes

Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)

Percentage of patients experiencing a DLT, defined as an adverse event or clinically significant abnormal laboratory value that is at least possibly related to study drugs and is not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness

Time frame: DLT period of 28 days

Phase 2: Overall Response Rate (ORR)

Percentage of patients with a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1)