An Open-Label, Phase 2 Trial of Nanatinostat in Combination with Valganciclovir in Patients with Epstein-Barr Virus-Positive (EBV+) Relapsed/Refractory Lymphomas (NAVAL-1)

Viracta Therapeutics

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Nanatinostat in combination with valganciclovir

Study type: Interventional

Funder types: Industry

Identifiers

NCT05011058

VT3996-202

Details and patient eligibility

About

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

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

Enrollment: 140 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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140 participants in 1 patient group

Nanatinostat with Valganciclovir

Experimental group

Description:

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.

Treatment:

Drug: Nanatinostat in combination with valganciclovir