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

Nasopharyngeal Carcinoma Clinical Trial

Official title:

An Open-Label, Multicenter Phase 1b/2 Study of Nanatinostat and Valganciclovir in Patients With Advanced Epstein-Barr Virus-Positive (EBV+) Solid Tumors and in Combination With Pembrolizumab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05166577
• Other study ID #: VT3996-301
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 8, 2021
• Est. completion date: October 2025

Study information

• Verified date: March 2024
• Source: Viracta Therapeutics, Inc.
• Contact: Afton Katkov, MSc
• Phone: 858-400-8470
• Email: ClinicalTrials[@]Viracta.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: October 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Related Conditions & MeSH terms

• Carcinoma
• EBV Related Carcinoma
• Leiomyosarcoma
• Nasopharyngeal Carcinoma
• Stomach Neoplasms

Intervention

Drug:
• Nanatinostat
Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week
• Nanatinostat
Nanatinostat at the confirmed RP2D
• Valganciclovir
Valganciclovir starting at 900 mg orally daily
• Pembrolizumab
Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks

Locations

Country	Name	City	State
Australia	Blacktown Hospital	Blacktown
Australia	Macquarie University	Sydney
Canada	Princess Margaret Cancer Centre	Toronto
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Hong Kong United Oncology Centre	Kowloon
Hong Kong	Prince Of Wales Hospital, The Chinese University Of Hong Kong	Sha Tin
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St. Mary's Hospital	Seoul
Malaysia	University of Malaya Medical Centre	Kuala Lumpur
Malaysia	Sarawak General Hospital	Kuching	Sarawak
Malaysia	National Cancer Institute (Institut Kanser Negara)	Putrajaya
Singapore	National Cancer Centre Singapore	Singapore
Singapore	Tan Tock Seng Hospital	Singapore
Taiwan	Mackay Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei City
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Linkou Chang Gung Memorial Hospital	Taoyuan City
United States	University of Colorado Hospital	Aurora	Colorado
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The Oncology Institute of Hope and Innovation	Lynwood	California
United States	Stanford Cancer Center	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Viracta Therapeutics, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Hong Kong,  Korea, Republic of,  Malaysia,  Singapore,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b: Incidence of dose-limiting toxicities (DLTs)		DLT period of 28 Days
Primary	Phase 2: Overall response rate (ORR)		Approximately 3 years
Secondary	Incidence and severity of adverse events		Approximately 28 days following the last dose
Secondary	Duration of response (DOR)		Approximately 3 years
Secondary	Disease control rate (DCR)		Approximately 3 years
Secondary	Progression-free survival (PFS)		Approximately 3 years
Secondary	Overall survival (OS)		Approximately 3 years
Secondary	Pharmacokinetic parameter - time to maximum plasma concentration [tmax]		Approximately at 28 days following enrollment
Secondary	Pharmacokinetic parameter - maximum plasma concentration [Cmax]		Approximately 28 days following enrollment
Secondary	Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC]		Approximately 28 days following enrollment