An Open-Label Phase 2 Trial of Nanatinostat Plus Valganciclovir in Patients With EBV+ Relapsed/Refractory Lymphomas (NAVAL-1)

An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas

Study Overview

• Status: Terminated
• Conditions: EBV-Related Hodgkin Lymphoma; Epstein-Barr Virus Associated Lymphoma; EBV-Related PTLD; EBV-Related Lymphoproliferative Disorder; EBV-Positive DLBCL, NOS; EBV Related PTCL, NOS; EBV-Related Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Nanatinostat in combination with valganciclovir

Detailed Description

Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas:

1. Diffuse large B-cell lymphoma (DLBCL)
2. Extranodal natural killer/T-cell lymphoma (ENKTL)
3. Peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS)
4. Hodgkin lymphoma (HL)
5. Post-transplant lymphoproliferative disorders (PTLD)
6. Human immunodeficiency virus (HIV)-associated lymphomas (HIV-L)
7. EBV+ lymphomas other than the above

The study was terminated prematurely and did not reach its target enrollment.

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • The Alfred Hospital
    • Melbourne, Victoria, Australia
      • Box Hill Hospital
• Brazil
  • Joinville, Brazil
    • CEPEVILLE - Instituto Joinvilense de Hematologia e Oncologia
  • Rio De Janeiro, Brazil
    • Ruschel Medicina e Pesquisa Clínica
  • Santo André, Brazil
    • CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
  • São Paulo, Brazil
    • CIPE Centro Internacional de Pesquisa - AC Camargo Cancer Center
  • São Paulo, Brazil
    • HCFMUSP - Hospital das Clínicas da Faculdade de Medicina Universidade de São Paulo
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Cross Cancer Institute
  • British Columbia
    • Vancouver, British Columbia, Canada
      • BC Cancer Agency
  • Quebec
    • Montréal, Quebec, Canada
      • Hôpital Maisonneuve-Rosemont
• France
  • Paris, France
    • Henri Mondor University Hospital
  • Aquitaine
    • Bordeaux Cedex, Aquitaine, France
      • Institut Bergonie
  • Ile-de-France
    • Paris, Ile-de-France, France
      • Hôpital Universitaire Pitié Salpêtrière
  • Limousin
    • Limoges cedex, Limousin, France
      • Centre Hospitalier Universitaire Limoges
  • Nouvelle-Aquitaine
    • Pessac, Nouvelle-Aquitaine, France
      • Hôpital Haut-Lévêque
  • Rhone-Alps
    • Pierre-Bénite, Rhone-Alps, France
      • Centre hospitalier Lyon-Sud
• Germany
  • Leipzig, Germany
    • Universitätsklinikum Leipzig
  • Bavaria
    • Würzburg, Bavaria, Germany
      • Universitatsklinikum Wurzburg
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center, Ein Kerem Hospital
• Italy
  • Bologna, Italy
    • Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi
  • Brescia, Italy
    • Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
  • Milano, Italy
    • Istituto Europeo di Oncologia
  • Milano, Italy
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Pavia, Italy
    • Fondazione IRCCS Policlinico San Matteo
  • Reggio Emilia, Italy
    • Arcispedale Santa Maria Nuova
  • Roma, Italy
    • Fondazione Policlinico Universitario Agostino Gemelli
  • Milan
    • Rozzano, Milan, Italy
      • Istituto Clinico Humanitas
  • Pordenone
    • Aviano, Pordenone, Italy
      • Centro Di Riferimento Oncologico
• Korea, Republic of
  • Incheon, Korea, Republic of
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of
    • Samsung Medical Center
• Malaysia
  • Kuching, Malaysia
    • Sarawak General Hospital / Hospital Umum Sarawak
• Singapore
  • Singapore, Singapore
    • Singapore General Hospital
  • Singapore, Singapore
    • National Cancer Centre Singapore
  • Singapore, Singapore
    • Oncocare Cancer Center
• Spain
  • Barcelona, Spain
    • Hospitalet de Llobregat
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Jimenez Diaz Foundation University Hospital
• Taiwan
  • Kaohsiung, Taiwan
    • Kaohsiung Chang Gung Memorial Hospital
  • Kaohsiung, Taiwan
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Tainan, Taiwan
    • National Cheng Kung University Hospital
  • Taipei City, Taiwan
    • National Taiwan University Hospital
  • Taoyuan City, Taiwan
    • Chang Gung Memorial Hospital - Linkou Branch
• United Kingdom
  • Liverpool, United Kingdom
    • The Clatterbridge Cancer Centre NHS Foundation Trust
  • London, United Kingdom
    • University College London Hospitals Nhs Foundation Trust
  • Manchester, United Kingdom
    • The Christie Nhs Foundation Trust
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • The University of Alabama at Birmingham Comprehensive Cancer Center
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • Los Angeles, California, United States, 90095
      • David Geffen School of Medicine - UCLA
    • Orange, California, United States, 92868
      • University of California Irvine
    • San Diego, California, United States, 92103
      • Scripps MD Anderson Cancer Center
    • San Francisco, California, United States, 94143
      • UCSF Hematology and Blood and Marrow Transplant
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center: Hackensack Univeristy
  • New York
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University: Wexner Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center - Jefferson Health
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75235
      • Harold C. Simmons Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah, Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• EBV+ DLBCL, NOS and PTCL, NOS, and AITL: Relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent.
• For EBV+ PTLD patients: Relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-CD20 immunotherapy. For patients with EBV+ PTLD only, age 12 years and older and weighing greater than 40 kg (Adolescent, Adult, Older Adult) are allowed
• For other EBV+ relapsed/refractory lymphoma: Following at least 1 course of an anit-CD20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated)
• No available therapies in the opinion of the Investigator
• Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy
• Measurable disease per Cheson 2007
• ECOG performance status 0, 1, 2
• Adequate bone marrow function

Key Exclusion Criteria:

• Presence or history of CNS involvement by lymphoma
• Systemic anticancer therapy or CAR-T within 21 days
• Antibody (anticancer) agents within 28 days
• Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant
• Less than 90 days from prior allogeneic transplant.
• Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1
• 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 (excluding viral upper respiratory tract infections).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nanatinostat with Valganciclovir; Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily. Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.	Drug: Nanatinostat in combination with valganciclovir; Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles; Other Names: VRx-3996 in combination with Valcyte

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	Interval of time from date of first observed complete or partial response per 2007 International Working Group (IWG) criteria to the date of documented disease progression or death due to any cause, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. DOR was censored at the time of study withdrawal for hematopoietic stem cell transplant, or at the time of study termination, whichever was earlier, for patients whose disease was still in response.	Up to approximately 2 years
Time to Next Anti-Lymphoma Treatment (TTNLT)	Interval of time from the start of study drug treatment to the date of next anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy).	Up to approximately 3 years
Time to Progression (TTP)	Interval of time from the start of study drug treatment to the date of disease progression, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. TTP was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression.	Up to approximately 3 years
Progression-Free Survival (PFS)	Interval of time from the start of study drug treatment to the date of first documented disease progression (defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir), initiation of new antineoplastic therapy, or death from any cause, whichever occurred first. PFS was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression or death.	Up to approximately 3 years
Overall Survival (OS)	Interval of time from the start of study drug treatment to the date of death for any reason. OS was censored at the time of study withdrawal or study termination, whichever was earlier, for patients without reported death.	Up to approximately 3 years
Number (Percentage) of Participants With Adverse Events (AEs)	Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study	Up to approximately 2 years
Pharmacokinetic (PK) Parameter - Time to Maximum Plasma Concentration [Tmax]	Defined as the time required to reach peak plasma concentration [Cmax] after study drug administration	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)
Pharmacokinetic (PK) Parameter - Maximum Plasma Concentration [Cmax]	Defined as the peak plasma concentration [Cmax] after study drug administration	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)
Pharmacokinetic Parameter - 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 plasma concentration	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)
Pharmacokinetic (PK) Parameter - Half-Life [t1/2]	Defined as the time required to reduce plasma concentration by 50% after study drug administration	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) by Study Milestone in the Peripheral T-Cell Lymphoma (Combination Therapy) Cohort That Enrolled Patients Beyond Stage 1 or in the Peripheral T-Cell Lymphoma (Monotherapy) Cohort Who Crossed Over to Receive Combination Therapy	Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.	Up to approximately 2 years
Duration of Response (DOR) by Study Milestone in the Peripheral T-Cell Lymphoma (Combination Therapy) Cohort That Enrolled Patients Beyond Stage 1 or in the Peripheral T-Cell Lymphoma (Monotherapy) Cohort Who Crossed Over to Receive Combination Therapy	Interval of time from date of first observed complete or partial response per 2007 International Working Group (IWG) criteria to the date of documented disease progression or death due to any cause, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. DOR was censored at the time of study withdrawal for hematopoietic stem cell transplant, or at the time of study termination, whichever was earlier, for patients whose disease was still in response.	Up to approximately 2 years

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, Coiffier B, Fisher RI, Hagenbeek A, Zucca E, Rosen ST, Stroobants S, Lister TA, Hoppe RT, Dreyling M, Tobinai K, Vose JM, Connors JM, Federico M, Diehl V; International Harmonization Project on Lymphoma. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579-86. doi: 10.1200/JCO.2006.09.2403. Epub 2007 Jan 22.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2021
• Primary Completion (Actual): December 26, 2024
• Study Completion (Actual): January 31, 2025

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 18, 2021

Study Record Updates

• Last Update Posted (Actual): July 28, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Epstein-Barr virus (EBV); EBV-positive lymphomas; EBV-positive T-cell lymphoma; EBV-positive Hodgkin lymphoma; EBV-positive diffuse large B-cell lymphoma (DLBCL); EBV-positive extranodal natural killer/T-cell lymphoma; EBV-positive peripheral T-cell lymphoma (PTCL); EBV-positive post-transplant lymphoproliferative disorders
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Infections; Virus Diseases; Neoplasms by Histologic Type; DNA Virus Infections; Lymphatic Diseases; Immunoproliferative Disorders; Herpesviridae Infections; Tumor Virus Infections; Lymphoma; Hodgkin Disease; Lymphoproliferative Disorders; Epstein-Barr Virus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: VT3996-202

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