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

NCT05166577 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: VT3996-301
• Study Type: interventional
• Target: 26
• Locations: 8 countries
• Sites: 13

Brief Summary

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

Conditions

Nasopharyngeal Carcinoma; EBV-Related Gastric Carcinoma; EBV-Related Leiomyosarcoma; EBV Related Carcinoma; EBV-Related Sarcoma

Outcome Measures

Primary Outcomes (2)

• Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)

  Percentage of patients experiencing a DLT, defined as an adverse event or clinically significant abnormal laboratory value that is at least possibly related to study drugs and is not primarily related to disease, disease progression, concomitant medication(s), or intercurrent illness

  DLT period of 28 days

• Phase 2: Overall Response Rate (ORR)

  Percentage of patients with a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 (v1.1)

  Approximately 3 years

Secondary Outcomes (13)

• Incidence of Adverse Events

  Approximately 3 years

• Phase 2: Duration of Response (DOR)

  Approximately 3 years

• Phase 2: Disease Control Rate (DCR)

  Approximately 3 years

• Phase 2: Progression-Free Survival (PFS)

  Approximately 3 years

• Phase 2: Overall Survival (OS)

  Approximately 3 years

Study Arms (2)

Nanatinostat in combination with valganciclovir

EXPERIMENTAL

Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, and valganciclovir starting at 900 mg orally daily, then Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 dose

Drug: Nanatinostat; Drug: Valganciclovir

Nanatinostat in combination with valganciclovir and pembrolizumab

EXPERIMENTAL

Phase 2: Nanatinostat and valganciclovir at the confirmed recommended Phase 2 doses in combination with pembrolizumab 200 mg intravenous (IV) every 3 weeks

Drug: Nanatinostat; Drug: Valganciclovir; Drug: Pembrolizumab

Interventions

Nanatinostat DRUG

Phase 1b: Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week, then Phase 2: Nanatinostat at the confirmed recommended Phase 2 dose

Also known as: VRx-3996

Nanatinostat in combination with valganciclovir; Nanatinostat in combination with valganciclovir and pembrolizumab

Valganciclovir DRUG

Phase 1b: Valganciclovir starting at 900 mg orally daily, then Phase 2: Valganciclovir at the confirmed recommended Phase 2 dose

Also known as: Valcyte

Nanatinostat in combination with valganciclovir; Nanatinostat in combination with valganciclovir and pembrolizumab

Pembrolizumab DRUG

Phase 2: Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks

Also known as: Keytruda

Nanatinostat in combination with valganciclovir and pembrolizumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Viracta Therapeutics, Inc.: lead

Study Sites (13)

Stanford Cancer Center

Stanford, California, 94305, United States

Location

University of Colorado Hospital

Aurora, Colorado, 80045, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Blacktown Hospital

Blacktown, Australia

Location

Princess Margaret Cancer Centre

Toronto, Canada

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince Of Wales Hospital, The Chinese University Of Hong Kong

Shatin, Hong Kong

Location

Sarawak General Hospital

Kuching, Sarawak, Malaysia

Location

University of Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

National Cancer Centre Singapore

Singapore, Singapore

Location

Samsung Medical Center

Seoul, South Korea

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan, Taiwan

Location

MeSH Terms

Conditions

Nasopharyngeal Carcinoma

Interventions

Valganciclovir; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Nasopharyngeal Neoplasms; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Nasopharyngeal Diseases; Pharyngeal Diseases; Stomatognathic Diseases; Otorhinolaryngologic Diseases

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 prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.

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 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A traditional 3+3 dose escalation design followed first by a dose optimization cohort and then by dose expansion with 1:1 randomization to receive nanatinostat and valganciclovir with or without pembrolizumab in Phase 2. The study was prematurely terminated after the end of Phase 1b and did not proceed to Phase 2.

Study Record Dates

• First Submitted: December 3, 2021
• First Posted: December 22, 2021
• Study Start: October 8, 2021
• Primary Completion: October 30, 2024
• Study Completion: January 10, 2025
• Last Updated: March 12, 2025
• Results First Posted: February 24, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); MY (2); AU (1); CA (1); HK (2); SG (1); US (3); TW (2)