Clinical trial NCT05166577: Nanatinostat Plus Valganciclovir in Advanced EBV+ Solid Tumors and in Combination With Pembrolizumab in EBV+ RM-NPC
Official title: Open-Label Multicenter Phase 1b/2 Study of Nanatinostat + Valganciclovir in Patients With Advanced Epstein-Barr Virus-Positive Solid Tumors and in Combination With Pembrolizumab in Patients With Recurrent/Metastatic Nasopharyngeal Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Nasopharyngeal Carcinoma
EBV-Related Gastric Carcinoma
EBV-Related Leiomyosarcoma
EBV Related Carcinoma
EBV-Related Sarcoma
Lead sponsor: Viracta Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-12-22
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1b: Incidence of Dose-Limiting Toxicities (DLTs)
timeFrame: DLT period of 28 days
measure: Phase 2: Overall Response Rate (ORR)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Incidence of Adverse Events
timeFrame: Approximately 3 years
measure: Phase 2: Duration of Response (DOR)
timeFrame: Approximately 3 years
measure: Phase 2: Disease Control Rate (DCR)
timeFrame: Approximately 3 years
measure: Phase 2: Progression-Free Survival (PFS)
timeFrame: Approximately 3 years
measure: Phase 2: Overall Survival (OS)
timeFrame: Approximately 3 years
measure: Pharmacokinetic Parameter (Nanatinostat) - Time to Maximum Plasma Concentration [Tmax]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Ganciclovir) - Time to Maximum Plasma Concentration [Tmax]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Nanatinostat) - Maximum Plasma Concentration [Cmax]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Ganciclovir) - Maximum Plasma Concentration [Cmax]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Nanatinostat) - Area Under the Plasma Concentration-Time Curve [AUC0-t]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Ganciclovir) - Area Under the Plasma Concentration-Time Curve [AUC0-t]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Nanatinostat) - Half-Life of Nanatinostat [t1/2]
timeFrame: Approximately 28 days following enrollment
measure: Pharmacokinetic Parameter (Ganciclovir) - Half-Life of Ganciclovir [t1/2]
timeFrame: Approximately 28 days following enrollment
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Sha Tin
country: Hong Kong
facility: Prince Of Wales Hospital, The Chinese University Of Hong Kong
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Kuching
country: Malaysia
facility: Sarawak General Hospital
state: Sarawak
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
city: Taoyuan City
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital
Study officials:
affiliation: Viracta Therapeutics
name: Darrel P Cohen, MD, PhD
role: STUDY_DIRECTOR
References: