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

March 26, 2024 updated by: Viracta Therapeutics, Inc.

An Open-Label, Multicenter Phase 1b/2 Study of Nanatinostat and Valganciclovir in Patients With Advanced Epstein-Barr Virus-Positive (EBV+) 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

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nanatinostat in combination with valganciclovir
Drug: Nanatinostat
Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week
Other Names:
  • VRx-3996
Drug: Valganciclovir
Valganciclovir starting at 900 mg orally daily
Other Names:
  • Valcyte
Drug: Nanatinostat
Nanatinostat at the confirmed RP2D
Other Names:
  • VRx-3996
Experimental: Nanatinostat in combination with valganciclovir and pembrolizumab
Drug: Nanatinostat
Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week
Other Names:
  • VRx-3996
Drug: Valganciclovir
Valganciclovir starting at 900 mg orally daily
Other Names:
  • Valcyte
Drug: Pembrolizumab
Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks
Other Names:
  • Keytruda
Drug: Nanatinostat
Nanatinostat at the confirmed RP2D
Other Names:
  • VRx-3996

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Phase 1b: Incidence of dose-limiting toxicities (DLTs)
Time Frame: DLT period of 28 Days
DLT period of 28 Days
Phase 2: Overall response rate (ORR)
Time Frame: Approximately 3 years
Approximately 3 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: Approximately 3 years
Approximately 3 years
Duration of response (DOR)
Time Frame: Approximately 3 years
Approximately 3 years
Disease control rate (DCR)
Time Frame: Approximately 3 years
Approximately 3 years
Incidence and severity of adverse events
Time Frame: Approximately 28 days following the last dose
Approximately 28 days following the last dose
Progression-free survival (PFS)
Time Frame: Approximately 3 years
Approximately 3 years
Pharmacokinetic parameter - time to maximum plasma concentration [tmax]
Time Frame: Approximately at 28 days following enrollment
Approximately at 28 days following enrollment
Pharmacokinetic parameter - maximum plasma concentration [Cmax]
Time Frame: Approximately 28 days following enrollment
Approximately 28 days following enrollment
Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC]
Time Frame: Approximately 28 days following enrollment
Approximately 28 days following enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Viracta Therapeutics, Inc.

Investigators

  • Study Director: Darrel P Cohen, MD, PhD, Viracta Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 8, 2021

Primary Completion (Estimated)

December 1, 2024

Study Completion (Estimated)

October 1, 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 28, 2024

Last Update Submitted That Met QC Criteria

March 26, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Nasopharyngeal Carcinoma

Clinical Trials on Nanatinostat

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Estonia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe