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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05166577
Recruitment Status : Recruiting
First Posted : December 22, 2021
Last Update Posted : June 22, 2022
Sponsor:
Information provided by (Responsible Party):
Viracta Therapeutics, Inc.

Brief Summary:
This study will evaluate the safety 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

Condition or disease Intervention/treatment Phase
Nasopharyngeal Carcinoma EBV-Related Gastric Carcinoma EBV-Related Leiomyosarcoma EBV Related Carcinoma EBV-Related Sarcoma Drug: Nanatinostat Drug: Pembrolizumab Drug: Valganciclovir Phase 1 Phase 2

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. In Phase 2, up to sixty patients with EBV+ RM-NPC will be randomized to receive nanatinostat in combination with valganciclovir at the RP2D with or without pembrolizumab, to evaluate safety, overall response rate, and potential pharmacodynamic markers. Additionally, patients with other EBV+ solid tumors will be enrolled to receive nanatinostat in combination with valganciclovir at the RP2D in a Phase 1b dose expansion cohort.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 88 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: A traditional 3+3 dose escalation design followed by a Phase 2 expansion randomized 1:1 to receive nantinostat and valganciclovir with or without pembrolizumab
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 7, 2021
Estimated Primary Completion Date : May 2024
Estimated Study Completion Date : March 2025


Arm Intervention/treatment
Experimental: Nanatinostat in combination with valganciclovir Drug: Nanatinostat
Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week
Other Name: VRx-3996

Drug: Valganciclovir
Valganciclovir 900 mg orally daily
Other Name: Valcyte

Experimental: Nanatinostat in combination with valganciclovir and pembrolizumab Drug: Nanatinostat
Nanatinostat dose escalation starting at 20 mg orally daily, 4 days per week
Other Name: VRx-3996

Drug: Pembrolizumab
Pembrolizumab (anti-PD-1) dosed at 200 mg intravenous (IV) every 3 weeks
Other Name: Keytruda

Drug: Valganciclovir
Valganciclovir 900 mg orally daily
Other Name: Valcyte




Primary Outcome Measures :
  1. Phase 1b: Incidence of dose-limiting toxicities (DLTs) [ Time Frame: DLT period of 28 Days ]
  2. Phase 2: Overall response rate (ORR) [ Time Frame: Approximately 3 years ]

Secondary Outcome Measures :
  1. Incidence and severity of adverse events [ Time Frame: Approximately 28 days following the last dose ]
  2. Duration of response (DOR) [ Time Frame: Approximately 3 years ]
  3. Disease control rate (DCR) [ Time Frame: Approximately 3 years ]
  4. Progression-free survival (PFS) [ Time Frame: Approximately 3 years ]
  5. Overall survival (OS) [ Time Frame: Approximately 3 years ]
  6. Pharmacokinetic parameter - time to maximum plasma concentration [tmax] [ Time Frame: Approximately at 28 days following enrollment ]
  7. Pharmacokinetic parameter - maximum plasma concentration [Cmax] [ Time Frame: Approximately 28 days following enrollment ]
  8. Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC] [ Time Frame: Approximately 28 days following enrollment ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05166577


Contacts
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Contact: Afton Katkov, MSc 858-400-8470 ClinicalTrials@Viracta.com

Locations
Show Show 19 study locations
Sponsors and Collaborators
Viracta Therapeutics, Inc.
Investigators
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Study Director: Lisa Rojkjaer, MD Viracta Therapeutics
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Responsible Party: Viracta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT05166577    
Other Study ID Numbers: VT3996-301
First Posted: December 22, 2021    Key Record Dates
Last Update Posted: June 22, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Carcinoma
Nasopharyngeal Carcinoma
Leiomyosarcoma
Stomach Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Neoplasms, Connective and Soft Tissue
Nasopharyngeal Neoplasms
Pharyngeal Neoplasms
Otorhinolaryngologic Neoplasms
Head and Neck Neoplasms
Neoplasms by Site
Nasopharyngeal Diseases
Pharyngeal Diseases
Stomatognathic Diseases
Otorhinolaryngologic Diseases
Neoplasms, Muscle Tissue
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases
Valganciclovir
Pembrolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents