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

• ClinicalTrials.gov Identifier: NCT03397706
• Recruitment Status: Recruiting
• First Posted: January 12, 2018
• Last Update Posted: July 28, 2021
• Sponsor: Viracta Therapeutics, Inc.
• Information provided by (Responsible Party): Viracta Therapeutics, Inc.

Tracking Information

• First Submitted Date: December 20, 2017
• First Posted Date: January 12, 2018
• Last Update Posted Date: July 28, 2021
• Actual Study Start Date: March 29, 2018
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2021)

• Incidence of adverse events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion [ Time Frame: Up to approximately 2 years ]
  Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
• Incidence of Dose Limiting Toxicities in Dose Escalation and Cohort Expansion [ Time Frame: Up to approximately 2 years ]
• ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Up to approximately 2 years ]

Original Primary Outcome Measures (submitted: January 10, 2018)

• Incidence of Adverse Events and changes in clinical safety laboratory values in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
  Determination of a safe and tolerable Recommended Phase 2 Dose (RP2D)
• Incidence of Dose Limiting Toxicities in in Dose Escalation and Cohort Expansion [ Time Frame: Approximately 2 years ]
  Determine safety and tolerability
• ORR as measured by stable disease (SD), partial response (PR), and complete response (CR) by radiographic assessment [ Time Frame: Approximately 2 years ]
  Disease response will be assessed using a combination of physical exam and imaging

Current Secondary Outcome Measures (submitted: May 7, 2021)

• Single-dose and steady-state Cmax of VRx-3996 and valganciclovir [ Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days) ]
  PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15
• Single-dose and steady-state AUC of VRx-3996 and valganciclovir [ Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days) ]
  PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2 ,C1D15, and C2D15
• Steady-state elimination half-life of VRx-3996 and valganciclovir [ Time Frame: Through Cycle 2 Day 15 (each cycle is 28 days) ]
  PK assessment of both VRx-3996 and valganciclovir pre-dose and at hours 0.5, 1, 2, 4, and 6 post-dose on C1 and C2D1 and pre-dose and at hour 2 on C1D2, C1D15, and C2D15
• Time to response [ Time Frame: Approximately 6 months ]
  The time from the start of first study drug administration to the first overall tumor response observed for subjects who achieved a CR or PR
• Duration of response [ Time Frame: Up to approximately 2 years ]
  The time interval (days) from date of the first overall response (CR or PR; achieved after study drug administration) to the date of disease progression
• Progression-free survival [ Time Frame: Up to approximately 2 years ]
  The interval between the date of first study drug administration and the date of PD or death, whichever is first reported

Original Secondary Outcome Measures (submitted: January 10, 2018)

• Single-dose and steady-state Cmax of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
  PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
• Single-dose and steady-state AUC of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
  PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
• Steady-state Elimination half-life of VRx-3996 and valganciclovir [ Time Frame: Through study completion, an average of 6 months ]
  PK assessment of both VRx-3996 and valganciclovir at 0, 1, 1.5, 2, 3, 5 and 7 hours post-dose on C1D1 and pre-dose on Day 1 of all following cycles
• Time to response [ Time Frame: Approximately 6 months ]
  The time from the start of first study drug administration to the first overall tumor response observed for subjects who achieved a CR or PR
• Duration of response [ Time Frame: Up to approximately 2 years ]
  The time interval (days) from date of the first overall response (CR or PR; achieved after the study drug administration) to the date of disease progression
• Progression-free survival [ Time Frame: Up to approximately 2 years ]
  The interval between the date of first study drug administration and the date of PD or death, whichever is first reported

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Dose Escalation & Expansion Study of Oral VRx-3996 & Valganciclovir in Subjects With EBV-Associated Lymphoid Malignancies
• Official Title: A Phase 1b/2 Open-Label, Dose Escalation & Expansion Study of Orally Administered VRx-3996 & Valganciclovir in Subjects With Epstein-Barr Virus-Associated Lymphoid Malignancies
• Brief Summary: 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 EBV+ lymphomas.
• 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 PK cohort to investigate the PK parameters of the tablet formulation.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Phase 1: dose escalation phase (3+3 design with definitions of dose limiting toxicity) to define a recommended phase 2 dose

Phase 2: dose expansion

PK Cohort

Masking: None (Open Label)
Primary Purpose: Treatment

Condition

• Epstein-Barr Virus Associated Lymphoma
• Lymphoproliferative Disorders

Intervention

• Drug: VRx-3996
  Taken orally once or twice daily
  Other Name: Nanatinostat
• Drug: Valganciclovir
  Taken orally once or twice daily

Study Arms

• 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

  Interventions:

  • Drug: VRx-3996
  • Drug: Valganciclovir
• Experimental: Phase 2 Dose Expansion
  VRx-3996 (RP2D: recommended phase 2 dose) and valganciclovir
  Interventions:

  • Drug: VRx-3996
  • Drug: Valganciclovir
• Experimental: PK Cohort
  Assessment of VRx-3996 tablet and valganciclovir PK parameters at the RP2D
  Interventions:

  • Drug: VRx-3996
  • Drug: Valganciclovir

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: May 7, 2021): 65
• Original Estimated Enrollment (submitted: January 10, 2018): 45
• Estimated Study Completion Date: December 2022
• Estimated Primary Completion Date: December 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Relapsed/refractory, pathologically confirmed 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 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 qPCR
• Known history of HHV-6 chromosomal integration
• Known history of HIV infection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Robert McRae, Vice President, Operations; 858-400-8470; ClinicalTrials@Viracta.com

• Listed Location Countries: Brazil, United States

Administrative Information

• NCT Number: NCT03397706
• Other Study ID Numbers: VT3996-201
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Viracta Therapeutics, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Viracta Therapeutics, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Robert McRae; Viracta Therapeutics

• PRS Account: Viracta Therapeutics, Inc.
• Verification Date: July 2021