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

NCT ID: NCT05166577

Last Updated: 2025-03-12

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-10-08

Study Completion Date

2025-01-10

Brief Summary

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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

Detailed Description

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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.

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

A traditional 3+3 dose escalation design followed first by a dose optimization cohort and then by dose expansion with 1:1 randomization to receive nanatinostat and valganciclovir with or without pembrolizumab in Phase 2.

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

TREATMENT

Blinding Strategy

NONE

Study Groups

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Nanatinostat in combination with valganciclovir

Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, and valganciclovir starting at 900 mg orally daily, then Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 dose

Group Type EXPERIMENTAL

Nanatinostat

Intervention Type DRUG

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

Valganciclovir

Intervention Type DRUG

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

Nanatinostat in combination with valganciclovir and pembrolizumab

Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 doses in combination with pembrolizumab 200 mg intravenous (IV) every 3 weeks

Group Type EXPERIMENTAL

Nanatinostat

Intervention Type DRUG

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

Valganciclovir

Intervention Type DRUG

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

Pembrolizumab

Intervention Type DRUG

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

Interventions

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Nanatinostat

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

Intervention Type DRUG

Valganciclovir

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

Intervention Type DRUG

Pembrolizumab

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

Intervention Type DRUG

Other Intervention Names

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VRx-3996 Valcyte Keytruda

Eligibility Criteria

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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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Viracta Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Darrel P Cohen, MD, PhD

Role: STUDY_DIRECTOR

Viracta Therapeutics

Locations

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Stanford Cancer Center

Stanford, California, United States

Site Status

University of Colorado Hospital

Aurora, Colorado, United States

Site Status

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

Blacktown Hospital

Blacktown, , Australia

Site Status

Princess Margaret Cancer Centre

Toronto, , Canada

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Prince Of Wales Hospital, The Chinese University Of Hong Kong

Shatin, , Hong Kong

Site Status

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Site Status

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Site Status

National Cancer Centre Singapore

Singapore, , Singapore

Site Status

Samsung Medical Center

Seoul, , South Korea

Site Status

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status

Linkou Chang Gung Memorial Hospital

Taoyuan, , Taiwan

Site Status

Countries

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United States Australia Canada Hong Kong Malaysia Singapore South Korea Taiwan

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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VT3996-301

Identifier Type: -

Identifier Source: org_study_id

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