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

NCT05011058 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: VT3996-202
• Study Type: interventional
• Target: 102
• Locations: 14 countries
• Sites: 62

Brief Summary

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

Conditions

Epstein-Barr Virus Associated Lymphoma; EBV-Positive DLBCL, NOS; EBV-Related Non-Hodgkin Lymphoma; EBV Related PTCL, NOS; EBV-Related Hodgkin Lymphoma; EBV-Related PTLD; EBV-Related Lymphoproliferative Disorder

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Duration of Response (DOR)

  Up to approximately 2 years

• Time to Next Anti-Lymphoma Treatment (TTNLT)

  Up to approximately 3 years

• Time to Progression (TTP)

  Up to approximately 3 years

• Progression-Free Survival (PFS)

  Up to approximately 3 years

• Overall Survival (OS)

  Up to approximately 3 years

Other Outcomes (2)

• 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

  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

  Up to approximately 2 years

Study Arms (1)

Nanatinostat with Valganciclovir

EXPERIMENTAL

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

Interventions

Nanatinostat in combination with valganciclovir DRUG

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

Also known as: VRx-3996 in combination with Valcyte

Nanatinostat with Valganciclovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Viracta Therapeutics, Inc.: lead

Study Sites (62)

The University of Alabama at Birmingham Comprehensive Cancer Center

Birmingham, Alabama, 35233, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

David Geffen School of Medicine - UCLA

Los Angeles, California, 90095, United States

Location

University of California Irvine

Orange, California, 92868, United States

Location

Scripps MD Anderson Cancer Center

San Diego, California, 92103, United States

Location

UCSF Hematology and Blood and Marrow Transplant

San Francisco, California, 94143, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

John Theurer Cancer Center: Hackensack Univeristy

Hackensack, New Jersey, 07601, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Ohio State University: Wexner Medical Center

Columbus, Ohio, 43210, United States

Location

Sidney Kimmel Cancer Center - Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Harold C. Simmons Comprehensive Cancer Center

Dallas, Texas, 75235, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Utah, Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Box Hill Hospital

Melbourne, Victoria, Australia

Location

The Alfred Hospital

Melbourne, Victoria, Australia

Location

CEPEVILLE - Instituto Joinvilense de Hematologia e Oncologia

Joinville, Brazil

Location

Ruschel Medicina e Pesquisa Clinica

Rio de Janeiro, Brazil

Location

CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia

Santo André, Brazil

Location

CIPE Centro Internacional de Pesquisa - AC Camargo Cancer Center

São Paulo, Brazil

Location

HCFMUSP - Hospital das Clínicas da Faculdade de Medicina Universidade de São Paulo

São Paulo, Brazil

Location

Cross Cancer Institute

Edmonton, Alberta, Canada

Location

BC Cancer Agency

Vancouver, British Columbia, Canada

Location

Hôpital Maisonneuve-Rosemont

Montreal, Quebec, Canada

Location

Institut Bergonié

Bordeaux, Aquitaine, France

Location

Centre Hospitalier Universitaire Limoges

Limoges, Limousin, France

Location

Hôpital Haut-Lévêque

Pessac, Nouvelle-Aquitaine, France

Location

Centre Hospitalier Lyon-Sud

Pierre-Bénite, Rhone-Alps, France

Location

Henri Mondor University Hospital

Paris, France

Location

Hôpital Universitaire Pitié Salpêtrière

Paris, Île-de-France Region, France

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Germany

Location

Hadassah Medical Center, Ein Kerem Hospital

Jerusalem, Israel

Location

Istituto Clinico Humanitas

Rozzano, Milan, Italy

Location

Centro di Riferimento Oncologico

Aviano, Pordenone, Italy

Location

Azienda Ospedaliero-Universitaria di Bologna Policlinico Sant Orsola-Malpighi

Bologna, Italy

Location

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

Brescia, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Istituto Europeo di Oncologia

Milan, Italy

Location

Fondazione IRCCS Policlinico San Matteo

Pavia, Italy

Location

Arcispedale Santa Maria Nuova

Reggio Emilia, Italy

Location

Fondazione Policlinico Universitario Agostino Gemelli

Roma, Italy

Location

Sarawak General Hospital / Hospital Umum Sarawak

Kuching, Malaysia

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Oncocare Cancer Center

Singapore, Singapore

Location

Singapore General Hospital

Singapore, Singapore

Location

Gachon University Gil Medical Center

Incheon, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Hospitalet de Llobregat

Barcelona, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Jimenez Diaz Foundation University Hospital

Madrid, Spain

Location

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, Taiwan

Location

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Location

National Cheng Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital - Linkou Branch

Taoyuan, Taiwan

Location

The Clatterbridge Cancer Centre NHS Foundation Trust

Liverpool, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 17242396 BACKGROUND

• Haverkos B, Alpdogan O, Baiocchi R, Brammer JE, Feldman TA, Capra M, Brem EA, Nair S, Scheinberg P, Pereira J, Shune L, Joffe E, Young P, Spruill S, Katkov A, McRae R, Royston I, Faller DV, Rojkjaer L, Porcu P. Targeted therapy with nanatinostat and valganciclovir in recurrent EBV-positive lymphoid malignancies: a phase 1b/2 study. Blood Adv. 2023 Oct 24;7(20):6339-6350. doi: 10.1182/bloodadvances.2023010330.

  PMID: 37530631 DERIVED

MeSH Terms

Conditions

Pyloric Stenosis, Hypertrophic; Epstein-Barr Virus Infections

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Pyloric Stenosis; Gastric Outlet Obstruction; Stomach Diseases; Gastrointestinal Diseases; Digestive System Diseases; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

The study was terminated prematurely.

Results Point of Contact

• Title: Dr. Darrel Cohen
• Organization: Viracta Therapeutics

ClinicalTrials@Viracta.com

858-400-8470

Study Officials

• Darrel P Cohen, MD, PhD

  Viracta Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, single-arm study utilizing a basket trial design. The study was terminated prematurely and did not reach its target enrollment.

Study Record Dates

• First Submitted: August 2, 2021
• First Posted: August 18, 2021
• Study Start: May 28, 2021
• Primary Completion: December 26, 2024
• Study Completion: January 31, 2025
• Last Updated: July 28, 2025
• Results First Posted: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IT (9); IL (1); ES (3); CA (3); US (17); GB (3); TW (5); BR (5); FR (6); MY (1); DE (2); SG (3); KR (2); AU (2)