Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV+ Lymphoid Malignancies

A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered Viracta (VRx)-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies

A two part, Phase 1b/2 study to define a recommended Phase 2 dose of VRx-3996 in combination with valganciclovir (Phase 1b) designed to evaluate the efficacy of this combination in relapsed/refractory Epstein-Barr Virus Associated Lymphoma (EBV+ lymphomas).

Study Overview

• Status: Completed
• Conditions: Lymphoproliferative Disorders; Epstein-Barr Virus-Associated Lymphoma
• Intervention / Treatment: Combination product: VRx-3996 and valganciclovir

Detailed Description

The purpose of this study is to determine whether VRx-3996 in combination with valganciclovir is safe, determine the side effect profile, and to determine whether this therapy may help patients with EBV-related lymphomas. The study has two phases. Goals of the first phase include determining a safe and tolerable dose that can be administered in phase 2. Goals of the second phase include further evaluating the safety and tolerability of VRx-3996 in combination with valganciclovir, evaluating how the drugs are metabolized in the body, evaluating response rates and other exploratory objectives that will help the researchers evaluate how these drugs work in the body. Participants will receive daily oral doses of the two study drugs and will have multiple study visits where they will have blood collected, physical examinations, and other medical monitoring. Following completion of the Ph2, the study will enroll additional patients into a Tablet Pharmacokinetic (PK) cohort to investigate the PK parameters of the tablet formulation.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Brazil
  • BA
    • Salvador, BA, Brazil, 40110-090
      • Centro de Hematologia e Oncologia da Bahia (CEHON)
  • PE
    • Recife, PE, Brazil, 50040-000
      • Hospital de Cancer de Pernambuco (HCP)
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil
      • Hospital do Câncer Mãe de Deus
  • SP
    • São Paulo, SP, Brazil, 08270-070
      • Hospital Santa Marcelina
    • São Paulo, SP, Brazil, 01321-001
      • Real e Benemerita Associacao Portuguesa de Beneficencia
    • São Paulo, SP, Brazil, 05403-000
      • Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (HC-FMUSP)
• United States
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • Los Angeles, California, United States, 90404
      • University of California, Los Angeles
    • Orange, California, United States, 92868
      • UC Irvine Chao Family Comprehensive Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Anschutz Cancer Pavilion
  • Florida
    • Orange City, Florida, United States, 32763
      • Mid Florida Hematology and Oncology Center
    • Weeki Wachee, Florida, United States, 34607
      • Asclepes Research Centers
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute, Emory University
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
    • Chicago, Illinois, United States, 60612
      • Ruth M Rothstein CORE Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indiana Blood and Marrow Transplantation
  • Kansas
    • Westwood, Kansas, United States, 66205
      • The University of Kansas Cancer Center and Medical Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Montana
    • Billings, Montana, United States, 59102
      • St. Vincent Healthcare Cancer Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • John Theurer Cancer Center At Hackensack UMC
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10065
      • Weill Cornell Medical College - New York Presbyterian Hospital
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center James Cancer Hospital
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Sammons Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Relapsed/refractory, pathologically confirmed Epstein-Barr Virus positive (EBV+) lymphoid malignancy or lymphoproliferative disease
• Absence of available therapy with reasonable likelihood of cure or significant clinical benefit
• Adequate hematologic, hepatic and renal function as defined by laboratory assessment

Key Exclusion Criteria:

• Known primary central nervous system (CNS) lymphoma
• Known CNS metastases or leptomeningeal disease unless appropriately treated and neurologically stable for at least 4 weeks
• Active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy
• Refractory graft versus host disease (GvHD) not responding to treatment
• Known active hepatitis B virus infection
• Circulating hepatitis C virus on quantitative polymerase chain reaction (qPCR)
• Known history of human herpes virus (HHV)-6 chromosomal integration
• Known history of HIV infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1b Dose Escalation; VRx-3996 (cohort 1) and valganciclovir VRx-3996 (cohort 2) and valganciclovir VRx-3996 (cohort 3) and valganciclovir VRx-3996 (cohort 4) and valganciclovir VRx-3996 (cohort 5) and valganciclovir	Combination product: VRx-3996 and valganciclovir; second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396); Other Names: ganciclovir; nanatinostat; Chroma (CHR)-3996
Experimental: Phase 2 Expansion - Capsule; VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)	Combination product: VRx-3996 and valganciclovir; second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396); Other Names: ganciclovir; nanatinostat; Chroma (CHR)-3996
Experimental: Phase 2 Expansion - Tablet; VRx-3996 and valganciclovir at the recommended Phase 2 dose (RP2D)	Combination product: VRx-3996 and valganciclovir; second-generation histone deacetylase (HDAC) inhibitor, nanatinostat (previously referred to as either VRx-3996 or CHR-3396); Other Names: ganciclovir; nanatinostat; Chroma (CHR)-3996

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number (Proportion) 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
Number (Proportion) of Participants With Dose-Limiting Toxicities (DLTs) in Phase 1b	Number (percentage) of patients experiencing a DLT during the first cycle (28 days) of study treatment in Phase 1b, defined as an adverse event (AE) or clinically significant abnormal laboratory value that was at least possibly related to study drugs and was not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness. In addition, to be considered a DLT, the AE had to meet at least one of the following criteria: Grade 4 anemia unexplained by underlying disease; Grade 4 febrile neutropenia; Grade 4 neutropenia lasting >5 days; Any other Grade 4 hematologic toxicity (thrombocytopenia, neutropenia, febrile neutropenia, anemia) of any duration; Grade 4 or higher tumor lysis syndrome; Grade 3 or higher thrombocytopenia (with or without bleeding); Any requirement for platelet transfusion; Grade 3 or higher non-hematologic toxicity despite adequate supportive care; Results in a dose hold of >7 consecutive days	Cycle 1 (28 days)
Overall Response Rate	Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the Lugano 2014 criteria (Cheson, Bruce D. et al. J Clin Oncology 2014;32(27):3059-68), where CR included complete metabolic response (no/minimal fluorodeoxyglucose [FDG] uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions, and PR included partial metabolic response (reduced FDG uptake compared with baseline) or radiologic response (target lesions ≤ 50% decrease in the sum of the product of perpendicular diameters of up to 6 target measurable nodes and extranodal sites)	Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	Interval of time from date of first observed complete or partial response per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) to the date of documented disease progression or death due to any cause, where disease progression is defined by Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) as progressive metabolic disease (increase in fluorodeoxyglucose [FDG] uptake from baseline or new FDG-avid foci consistent with lymphoma) or progressive radiologic response (increase in the product of perpendicular diameters of a single node by ≥ 50% or emergence of a new lesion)	Up to approximately 2 years
Time to Response	Interval of time from the start of study drug treatment to the first documentation of CR or PR per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68)	Up to approximately 2 years
Progression-Free Survival	Interval of time from the date of first study drug administration to the documented date of disease progression or death, whichever occurred first, where disease progression is defined by Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68) as progressive metabolic disease (increase in fluorodeoxyglucose [FDG] uptake from baseline or new FDG-avid foci consistent with lymphoma) or progressive radiologic response (increase in the product of perpendicular diameters of a single node by ≥ 50% or emergence of a new lesion)	Up to approximately 2 years
Disease Control Rate	Number (percentage) of patients with CR, PR, or stable disease (SD) per Lugano 2014 criteria (Cheson BD et al. J Clin Oncology 2014;32(27):3059-68)	Up to approximately 2 years
Overall Survival	Interval of time from date of first study drug treatment to date of death, for any reason (patients without documentation of death at the time of analysis were censored at the date the patient was last known to be alive)	Up to approximately 2 years
Cmax (ng/mL) of VRx-3996	Pharmacokinetic (PK) assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on cycle 1 day 1 (C1D1) and cycle 2 day 2 (C2D1)	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
Cmax (ng/mL) of Valganciclovir	PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
Area Under Curve (AUC) 0-t of VRx-3996	PK assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
AUC 0-t of of Valganciclovir	PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
Half-life of VRx-3996	PK assessment of VRx-3996 pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1
Half-life of Valganciclovir	PK assessment of valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1D1 and C2D1	Phase 1b: Cycle 1 Day 1 and Phase 2: multiple doses through Cycle 2 Day 1

Collaborators and Investigators

• Sponsor: Viracta Therapeutics, Inc.
• Investigators: Study Director: Jill DeFratis Robinson, Viracta Therapeutics

Publications and helpful links

Helpful Links

• Viracta Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2018
• Primary Completion (Actual): April 1, 2023
• Study Completion (Actual): May 4, 2023

Study Registration Dates

• First Submitted: December 20, 2017
• First Submitted That Met QC Criteria: January 10, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: EBV-associated peripheral T-cell lymphoma; EBV-associated angioimmunoblastic T-cell lymphoma; EBV-associated diffuse large B-cell lymphoma; EBV-associated post-transplant lymphoproliferative disorder; EBV-associated extranodal NK/T-cell lymphoma; EBV-associated Hodgkin lymphoma; EBV-associated non-Hodgkin lymphoma
• 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; Lymphoproliferative Disorders; Epstein-Barr Virus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir; Ganciclovir
• Other Study ID Numbers: VT3996-201

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