An Open-Label Phase 2 Trial of Nanatinostat Plus Valganciclovir in Patients With EBV+ Relapsed/Refractory Lymphomas

Phase 2

Terminated

Conditions: Epstein-Barr Virus Associated Lymphoma
EBV-Positive DLBCL, NOS
EBV-Related Non-Hodgkin Lymphoma
EBV Related PTCL, NOS
EBV-Related Hodgkin Lymphoma
EBV-Related PTLD
EBV-Related Lymphoproliferative Disorder

Interventions: Drug: Nanatinostat in combination with valganciclovir

Registration Number: NCT05011058

Lead Sponsor: Viracta Therapeutics, Inc.

Brief Summary: A Phase 2 study to evaluate the efficacy of nanatinostat in combination with valganciclovir in patients with relapsed/refractory EBV-positive lymphomas

Detailed Description: Patients with EBV-associated lymphomas have inferior outcomes with standard-of-care therapies compared to those with EBV-negative disease. Nanatinostat is a selective class I HDAC inhibitor which induces EBV lytic phase protein generation, activating (val)ganciclovir to its cytotoxic form. This open-label, multicenter, multinational, single-arm, Phase 2 basket study employs a Simon's 2-stage design to allow termination of enrollment into cohorts where treatment appears futile, and will include the following cohorts of patients with EBV+ relapsed/refractory lymphomas:

1. Diffuse large B-cell lymphoma (DLBCL)

2. Extranodal natural killer/T-cell lymphoma (ENKTL)

3. Peripheral T-cell lymphoma (PTCL), including angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (PTCL-NOS)

4. Hodgkin lymphoma (HL)

5. Post-transplant lymphoproliferative disorders (PTLD)

6. Human immunodeficiency virus (HIV)-associated lymphomas (HIV-L)

7. EBV+ lymphomas other than the above

The study was terminated prematurely and did not reach its target enrollment.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 102

Inclusion Criteria

EBV+ DLBCL, NOS and PTCL, NOS, and AITL: Relapsed/refractory disease following 1 or more prior systemic therapy(ies) with curative intent.
For EBV+ PTLD patients: Relapsed/refractory disease following 1 prior therapy and must have received at least 1 course of an anti-CD20 immunotherapy. For patients with EBV+ PTLD only, age 12 years and older and weighing greater than 40 kg (Adolescent, Adult, Older Adult) are allowed
For other EBV+ relapsed/refractory lymphoma: Following at least 1 course of an anit-CD20 immunotherapy and at least 1 course of anthracycline-based chemotherapy (unless contraindicated)
No available therapies in the opinion of the Investigator
Not eligible for high-dose chemotherapy with allogeneic/autologous stem cell transplantation or CAR-T therapy
Measurable disease per Cheson 2007
ECOG performance status 0, 1, 2
Adequate bone marrow function

Key

Exclusion Criteria

Presence or history of CNS involvement by lymphoma
Systemic anticancer therapy or CAR-T within 21 days
Antibody (anticancer) agents within 28 days
Less than 60 days from prior autologous hematopoietic stem cell or solid organ transplant
Less than 90 days from prior allogeneic transplant.
Daily corticosteroids (≥20 mg of prednisone or equivalent) within week prior to Cycle 1 Day 1
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 (excluding viral upper respiratory tract infections).

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nanatinostat with Valganciclovir	Nanatinostat in combination with valganciclovir	Patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week with valganciclovir 900 mg orally once daily. Up to 10 PTCL patients will receive nanatinostat 20 mg orally once daily, days 1-4 per week.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	Up to approximately 2 years	Number (percentage) of patients with a best overall complete response (CR) or partial response (PR) according to the 2007 International Working Group (IWG) criteria, where CR included complete disappearance of all detectable clinical evidence of disease and disease-related symptoms if present before therapy with all lymph nodes and nodal masses having regressed on computed tomography to normal size, and PR included at least a 50% decrease in sum of the product of the diameters (SPD) of up to six of the largest dominant nodes or nodal masses, no increase should have been observed in the size of other nodes, liver, or spleen, and splenic and hepatic nodules must have regressed by ≥ 50% in their SPD or, for single nodules, in the greatest transverse diameter.

Secondary Outcome Measures

Name	Time	Method
Duration of Response (DOR)	Up to approximately 2 years	Interval of time from date of first observed complete or partial response per 2007 International Working Group (IWG) criteria to the date of documented disease progression or death due to any cause, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. DOR was censored at the time of study withdrawal for hematopoietic stem cell transplant, or at the time of study termination, whichever was earlier, for patients whose disease was still in response.
Time to Next Anti-Lymphoma Treatment (TTNLT)	Up to approximately 3 years	Interval of time from the start of study drug treatment to the date of next anti-lymphoma treatment (including chemotherapy, radiotherapy, radioimmunotherapy, or immunotherapy).
Time to Progression (TTP)	Up to approximately 3 years	Interval of time from the start of study drug treatment to the date of disease progression, where disease progression is defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir. TTP was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression.
Progression-Free Survival (PFS)	Up to approximately 3 years	Interval of time from the start of study drug treatment to the date of first documented disease progression (defined by 2007 IWG criteria as any new lesion or increase by ≥ 50% of previously involved sites from nadir), initiation of new antineoplastic therapy, or death from any cause, whichever occurred first. PFS was censored at the time of study withdrawal for hematopoietic stem cell transplant, at the time of study treatment withdrawal (or at the time of crossover from monotherapy to combination therapy), or at the time of study termination, whichever was earliest, for patients without reported disease progression or death.
Overall Survival (OS)	Up to approximately 3 years	Interval of time from the start of study drug treatment to the date of death for any reason. OS was censored at the time of study withdrawal or study termination, whichever was earlier, for patients without reported death.
Number (Percentage) of Participants With Adverse Events (AEs)	Up to approximately 2 years	Number (percentage) of patients experiencing at least one treatment-emergent adverse event, defined as those untoward medical events with onset after the first dose of study drug or existing events that worsened after the first dose during the study
Pharmacokinetic (PK) Parameter - Time to Maximum Plasma Concentration [Tmax]	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)	Defined as the time required to reach peak plasma concentration \[Cmax\] after study drug administration
Pharmacokinetic (PK) Parameter - Maximum Plasma Concentration [Cmax]	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)	Defined as the peak plasma concentration \[Cmax\] after study drug administration
Pharmacokinetic Parameter - Area Under the Plasma Concentration-Time Curve [AUC0-t]	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)	Defined as the area under the concentration-time curve from time 0 to the last measurable plasma concentration
Pharmacokinetic (PK) Parameter - Half-Life [t1/2]	Cycle 1 Day 1 and Cycle 6 Day 1 at pre-dose and 1, 2, 4, and 6 hours post-dose (each cycle was 28 days)	Defined as the time required to reduce plasma concentration by 50% after study drug administration

Trial Locations

Locations (62): The University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸
Birmingham, Alabama, United States
City of Hope
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Duarte, California, United States
David Geffen School of Medicine - UCLA
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Los Angeles, California, United States
University of California Irvine
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Orange, California, United States
Scripps MD Anderson Cancer Center
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San Diego, California, United States
UCSF Hematology and Blood and Marrow Transplant
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San Francisco, California, United States
University of Colorado Cancer Center
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Aurora, Colorado, United States
University of Maryland Medical Center
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Baltimore, Maryland, United States
John Theurer Cancer Center: Hackensack Univeristy
🇺🇸
Hackensack, New Jersey, United States
Icahn School of Medicine at Mount Sinai
🇺🇸
New York, New York, United States
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The University of Alabama at Birmingham Comprehensive Cancer Center
🇺🇸Birmingham, Alabama, United States