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

Phase 1

Terminated

• Conditions: Nasopharyngeal Carcinoma; EBV-Related Gastric Carcinoma; EBV-Related Leiomyosarcoma; EBV Related Carcinoma; EBV-Related Sarcoma
• Interventions: Drug: Nanatinostat; Drug: Valganciclovir; Drug: Pembrolizumab

• Registration Number: NCT05166577
• Lead Sponsor: Viracta Therapeutics, Inc.

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

Detailed Description

This is an open-label, multicenter Phase 1b/2 study evaluating nanatinostat in combination with valganciclovir alone and in combination with pembrolizumab. Nanatinostat is a selective class I HDAC inhibitor which induces EBV early lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form.

The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) in patients with EBV+ RM-NPC followed by a Project Optimus \| FDA (https://www.fda.gov/about-fda/oncology-center-excellence/project-optimus) cohort to confirm the RP2D. Up to 60 patients with EBV+ RM-NPC will be randomized 1:1 to receive nanatinostat in combination with valganciclovir at the confirmed RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers in the Phase 2 dose expansion part of the study. Additionally, patients with other EBV+ solid tumors will be enrolled to receive nanatinostat in combination with valganciclovir at the RP2D in a Phase 1b cohort.

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

Study Timeline

• Study Start: 2021-10-08
• Study First Submitted: 2021-12-03
• Study First Submitted QC: 2021-12-20
• Study First Posted: 2021-12-22
• Primary Completion: 2024-10-30
• Study Completion: 2025-01-10
• Results First Submitted: 2025-01-31
• Results First Submitted QC: 2025-01-31
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-21
• Results First Posted: 2025-02-24
• Last Update Posted: 2025-03-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• 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

Key

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)	DLT period of 28 days	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
Phase 2: Overall Response Rate (ORR)	Approximately 3 years	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)

Secondary Outcome Measures

Name	Time	Method
Incidence of Adverse Events	Approximately 3 years	Percentage of patients experiencing at least one treatment-emergent adverse event (AE), defined as those AEs with onset after the first dose of study drug or existing events that worsened after the first dose during the study
Phase 2: Duration of Response (DOR)	Approximately 3 years	Interval of time from the date of first observed CR or PR to the date of documented disease progression or death due to any cause, whichever occurs first
Phase 2: Disease Control Rate (DCR)	Approximately 3 years	Percentage of patients having a CR, PR, or stable disease at any time during treatment
Phase 2: Progression-Free Survival (PFS)	Approximately 3 years	Interval of time from the start of study drug treatment to the date of first documented disease progression or death from any cause, whichever occurs first
Phase 2: Overall Survival (OS)	Approximately 3 years	Interval of time from the start of study drug treatment to date of death for any reason
Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax]	Approximately 28 days following enrollment	Defined as the time required to reach peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1
Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax]	Approximately 28 days following enrollment	Defined as the time required to reach peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1
Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax]	Approximately 28 days following enrollment	Defined as the peak plasma concentration \[Cmax\] after nanatinostat administration on Cycle 2 Day 1
Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax]	Approximately 28 days following enrollment	Defined as the peak plasma concentration \[Cmax\] after valganciclovir administration on Cycle 2 Day 1
Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t]	Approximately 28 days following enrollment	Defined as the area under the concentration-time curve from time 0 to the last measurable nanatinostat concentration on Cycle 2 Day 1
Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t]	Approximately 28 days following enrollment	Defined as the area under the concentration-time curve from time 0 to the last measurable ganciclovir concentration on Cycle 2 Day 1
Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2]	Approximately 28 days following enrollment	Defined as the time required to reduce nanatinostat plasma concentration by 50% after nanatinostat administration on Cycle 2 Day 1
Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2]	Approximately 28 days following enrollment	Defined as the time required to reduce ganciclovir plasma concentration by 50% after valganciclovir administration on Cycle 2 Day 1

Trial Locations

Locations (13)

Stanford Cancer Center; 🇺🇸 Stanford, California, United States

University of Colorado Hospital; 🇺🇸 Aurora, Colorado, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Blacktown Hospital; 🇦🇺 Blacktown, Australia

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Canada

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Prince Of Wales Hospital, The Chinese University Of Hong Kong; 🇭🇰 Sha Tin, Hong Kong

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of

Sarawak General Hospital; 🇲🇾 Kuching, Sarawak, Malaysia

University of Malaya Medical Centre; 🇲🇾 Kuala Lumpur, Malaysia

National Cancer Centre Singapore; 🇸🇬 Singapore, Singapore

Taipei Veterans General Hospital; 🇨🇳 Taipei City, Taiwan

Linkou Chang Gung Memorial Hospital; 🇨🇳 Taoyuan City, Taiwan