An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

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

Detailed Description
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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: EBV+ diffuse large B-cell lymphoma (DLBCL, NOS) Peripheral T-cell lymphoma (PTCL), including PTCL-NOS and AITL Post-transplant lymphoproliferative disorder (PTLD) EBV+ lymphoproliferative disorders other than the above, including Extranodal NK/T-cell lymphoma (ENKTL)

Official Title
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An Open-Label, Phase 2 Trial of Nanatinostat in Combination With Valganciclovir in Patients With Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas

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

Intervention / Treatment
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* Drug: Nanatinostat in combination with valganciclovir


Participation Criteria
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Eligibility Criteria
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Key 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is an open-label, single-arm study utilizing a basket trial design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nanatinostat with Valganciclovir<br>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. | Drug: Nanatinostat in combination with valganciclovir<br>* Drug: Nanatinostat, 20 mg orally once daily, 4 days per week in 28 day cycles Other name: VRx-3996 Drug: Valganciclovir, 900 mg orally once daily in 28 day cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Assessed by an Independent Review Committee (IRC) per the 2007 International Working Group Response Criteria (IWGRC) | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) |  | Approximately 3 years | 
| Time to next anti-lymphoma treatment (TTNLT) |  | Approximately 3 years | 
| Progression-free survival (PFS) |  | Approximately 3 years | 
| Time to progression (TTP) |  | Approximately 3 years | 
| Overall survival |  | Approximately 3 years | 
| Incidence and severity of treatment-emergent adverse events |  | Approximately 28 days following the last dose | 
| Pharmacokinetic parameter - time to maximum plasma concentration [tmax], |  | Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days) | 
| Pharmacokinetic parameter - maximum plasma concentration [Cmax] |  | Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days) | 
| Pharmacokinetic parameter - area under the plasma concentration-time curve [AUC] |  | Approximately 6 months following the end of Cycle 1 Day 1 (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EBV positive post-transplant lymphoproliferative disorder (PTLD), EBV lymphoma, Lymphoproliferative Disorders, Epstein-Barr Virus (EBV), EBV positive T cell lymphoma, EBV positive diffuse large B-cell lymphoma (DLBCL), EBV positive peripheral T-cell lymphoma (PTCL), EBV positive PTLD in Pediatrics