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

Study Overview

• Status: Terminated
• Conditions: Nasopharyngeal Carcinoma; EBV-Related Gastric Carcinoma; EBV-Related Leiomyosarcoma; EBV Related Carcinoma; EBV-Related Sarcoma
• Intervention / Treatment: Drug: Nanatinostat; Drug: Valganciclovir; Drug: Pembrolizumab

Detailed 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.

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

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Blacktown, Australia
    • Blacktown Hospital
• Canada
  • Toronto, Canada
    • Princess Margaret Cancer Centre
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Sha Tin, Hong Kong
    • Prince of Wales Hospital, the Chinese University of Hong Kong
• Korea, Republic of
  • Seoul, Korea, Republic of
    • Samsung Medical Center
• Malaysia
  • Kuala Lumpur, Malaysia
    • University of Malaya Medical Centre
  • Sarawak
    • Kuching, Sarawak, Malaysia
      • Sarawak General Hospital
• Singapore
  • Singapore, Singapore
    • National Cancer Centre Singapore
• Taiwan
  • Taipei City, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan City, Taiwan
    • Linkou Chang Gung Memorial Hospital
• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Other Names: VRx-3996; Drug: Valganciclovir; Phase 1b: Valganciclovir starting at 900 mg orally daily, then Phase 2: Valganciclovir at the confirmed recommended Phase 2 dose; Other Names: Valcyte
Experimental: 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	Drug: 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; Other Names: VRx-3996; Drug: Valganciclovir; Phase 1b: Valganciclovir starting at 900 mg orally daily, then Phase 2: Valganciclovir at the confirmed recommended Phase 2 dose; Other Names: Valcyte; Drug: Pembrolizumab; Phase 2: Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	Approximately 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events	Percentage of patients experiencing at least one treatment-emergent adverse event (AE), defined as those AEs with onset after the first dose of study drug or existing events that worsened after the first dose during the study	Approximately 3 years
Phase 2: Duration of Response (DOR)	Interval of time from the date of first observed CR or PR to the date of documented disease progression or death due to any cause, whichever occurs first	Approximately 3 years
Phase 2: Disease Control Rate (DCR)	Percentage of patients having a CR, PR, or stable disease at any time during treatment	Approximately 3 years
Phase 2: Progression-Free Survival (PFS)	Interval of time from the start of study drug treatment to the date of first documented disease progression or death from any cause, whichever occurs first	Approximately 3 years
Phase 2: Overall Survival (OS)	Interval of time from the start of study drug treatment to date of death for any reason	Approximately 3 years
Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax]	Defined as the time required to reach peak plasma concentration [Cmax] after nanatinostat administration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax]	Defined as the time required to reach peak plasma concentration [Cmax] after valganciclovir administration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax]	Defined as the peak plasma concentration [Cmax] after nanatinostat administration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax]	Defined as the peak plasma concentration [Cmax] after valganciclovir administration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t]	Defined as the area under the concentration-time curve from time 0 to the last measurable nanatinostat concentration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t]	Defined as the area under the concentration-time curve from time 0 to the last measurable ganciclovir concentration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2]	Defined as the time required to reduce nanatinostat plasma concentration by 50% after nanatinostat administration on Cycle 2 Day 1	Approximately 28 days following enrollment
Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2]	Defined as the time required to reduce ganciclovir plasma concentration by 50% after valganciclovir administration on Cycle 2 Day 1	Approximately 28 days following enrollment

Collaborators and Investigators

• Sponsor: Viracta Therapeutics, Inc.
• Investigators: Study Director: Darrel P Cohen, MD, PhD, Viracta Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 8, 2021
• Primary Completion (Actual): October 30, 2024
• Study Completion (Actual): January 10, 2025

Study Registration Dates

• First Submitted: December 3, 2021
• First Submitted That Met QC Criteria: December 20, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Otorhinolaryngologic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Nasopharyngeal Diseases; Pharyngeal Diseases; Sarcoma; Neoplasms, Connective and Soft Tissue; Neoplasms, Muscle Tissue; Nasopharyngeal Neoplasms; Nasopharyngeal Carcinoma; Stomach Neoplasms; Carcinoma; Leiomyosarcoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Anti-Infective Agents; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Valganciclovir; Pembrolizumab
• Other Study ID Numbers: VT3996-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No