EBV+ Lymphoma may be associated with inferior survival outcomes.

Identifying which of your patients have EBV+ tumors may provide a new personalized treatment option.

Learn more about the NAVAL-1 clinical trial evaluating an oral, first-in-class, investigational combination therapy for patients with EBV+ lymphoma.

Contact us to refer patients or if you have questions
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Lymphomas are the most common type of Epstein-Barr virus-positive (EBV+) cancers. There are currently no approved therapies targeting EBV+ lymphoma in the United States.

Incidence of EBV+ Lymphoma

Although the incidence of EBV positivity in lymphoma varies widely across subtypes, it is most commonly associated with T-and NK-cell lymphomas and PTLD.

EBV Positivity by Lymphoma Subtype2-6

Lymphoma Type
Percent Positivity
Extranodal NK/T-cell lymphoma (ENKTL)
100%
Angioimmunoblastic T-cell lymphoma (AITL)
70%-80%
Post-transplant lymphoproliferative disorder (PTLD)
60%-80%
Peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS)
25%-58%
Hodgkin lymphoma (HL)
20%-30%
Diffuse large B-cell lymphoma (DLBCL)
5%-10%

EBV Positivity May Have an Adverse Impact on Clinical Survival Outcomes in DLBCL, PTCL, and Hodgkin Lymphoma2-6

1) ViractaGraphs@2x copy
Diffuse Large B-cell Lymphoma

(Progression-Free Survival)

2
Peripheral T-cell Lymphoma

(Overall Survival)

3
Hodgkin's Lymphoma

(Failure-Free Survival)

About the NAVAL-1 Clinical Trial

The NAVAL-1 clinical trial is a global, pivotal phase 2, multicenter, open-label, single-arm basket study designed to evaluate the safety and efficacy of the all-oral combination of nanatinostat with valganciclovir in patients with relapsed/refractory (R/R) EBV+ lymphoma. The trial will evaluate 6 subtypes of lymphoma (PTCL; ENKTL; EBV+ DLBCL, NOS; PTLD; HIV-associated lymphoma; and Hodgkin lymphoma) with a seventh cohort that will capture patients with other types of EBV+ lymphoma.

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The Investigational All-Oral Drug Combination: "Kick and Kill” Mechanism of Action

The NAVAL-1 clinical trial represents a novel approach to the treatment of EBV+ lymphoma, using a combination of an oral class-I specific HDAC inhibitor (nanatinostat) with an oral antiviral (valganciclovir, an oral prodrug of ganciclovir).

  • EBV exists in a latent form in tumor cells. In that form, it is not susceptible to the cytotoxic activity of ganciclovir.
  • Nanatinostat induces EBV lytic activation and expression of the EBV BGLF4 protein kinase (the “Kick”).
  • This in turn activates ganciclovir via phosphorylation, resulting in ganciclovir-induced inhibition of viral and cellular DNA synthesis and apoptosis (the “Kill”).

Nana-val “Kick and Kill” Mechanism of Action

1 (1)-min

LATENCY

EBV latent in cancer cells.

Valganciclovir, antiviral prodrug of ganciclovir (GCV), is inactive without expression of viral protein kinase (PK)

2 (1)-min

THE KICK

Nanatinostat selectively and potently induces expression of EBV protein kinase (PK), which activates GCV into its cytotoxic form

3 (1)-min

THE KILL

Cytotoxic GCV inhibits DNA replication leading to apoptosis in EBV+ cancer cells

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Phase 1b/2 Study

In a previous Phase 1b/2 study, the combination of nanatinostat and valganciclovir was evaluated in 55 patients with a variety of relapsed/refractory EBV-associated lymphomas. Eligible patients had received 1 or more prior therapies, had measurable disease, and had exhausted all standard therapies.1

The regimen was generally well tolerated: the most common treatment-emergent adverse events were nausea (38%); thrombocytopenia (36%); neutropenia (34%); anemia and constipation (both 31%); creatinine elevation, diarrhea, and fatigue (all 26%); and decreased appetite (22%).

For the 43 evaluable patients, the ORR was 40% (CR 19%). Complete responses were reported in DLBCL, T- and NK-cell lymphomas, and IA-LPD, with a median duration of response of 10.4 months.

This investigational drug combination received FDA fast track designation for the treatment of R/R EBV+ lymphoid malignancies in 2019. In addition, this drug combination received 4 orphan drug designations from the FDA for plasmablastic lymphoma; PTLD; T-cell lymphoma; and EBV+ DLBCL, NOS.

NAVAL-1 Phase 2 Basket Study in Patients With R/R EBV+ Lymphoma

Key Eligibility Criteria

  • Adults ≥ 18 years
  • EBV+ relapsed/refractory lymphoma following 2 or more prior systemic therapies
  • For ENKTL and PTCL patients only: Relapsed/refractory disease following 1 or more prior systemic therapies. ENKTL patients must have failed an asparaginase-containing regimen. 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
  • No CNS involvement

NAVAL-1 Phase 2 Basket Study Design

This global clinical trial is seeking to enroll 6 subtypes of patients with EBV+ relapsed/refractory lymphomas, with a seventh cohort included for patients with other types of EBV+ lymphoma.

Stage 1
Multiple lymphoma subtypes

Stage 2

Extranodal NK/T (2L)
Peripheral T-cell (2L)
PTLD
EBV+ DLBCL, NOS
Hodgkin
HIV-associated
Other
Expand cohorts from Stage 1 meeting efficacy threshold
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold344
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold54
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold53
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold34
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold23
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold
Further expansion of promising cohorts with additional patients may support registration

Stage 1
Multiple lymphoma subtypes

Extranodal NK/T (2L)
Peripheral T-cell (2L)
PTLD
EBV+ DLBCL, NOS
Hodgkin
HIV-associated
Other

Stage 2

Expand cohorts from Stage 1 meeting efficacy threshold
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold344
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold54
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold53
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold34
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold23
Further expansion of promising cohorts with additional patients may support registration
Expand cohorts from Stage 1 meeting efficacy threshold
Further expansion of promising cohorts with additional patients may support registration

Participants Who Qualify and Enroll Will Receive:

  • The investigational oral drug combination and all study-related medical care at no charge
  • Close monitoring by physicians who specialize in virus-related lymphomas
  • Reimbursement for study-related expenses such as transportation (as needed)
  • The opportunity to advance medical knowledge of EBV+ lymphomas

Take Action

Ask questions about the trial and see if your patients may qualify:
clinicaltrials@viracta.com

For more information about the trial visit:
Clinicaltrials.gov

NAVAL-1 National Trial Reference Number [NCT05011058]

Phase 1b/2 National Trial Reference Number [NCT03397706]

US Trial Locations

References

  1. Haverkos BM, Alpdogan O, Baiocchi R, Brammer JE, Feldman TA, Capra M, et al. Nanatinostat (Nstat) and valganciclovir (VGCV) in relapsed/refractory (R/R) Epstein-Barr virus-positive (EBV+) lymphomas: final results from the Phase 1b/2 VT3996-201 study. Blood. 2021;138 (suppl 1):623. doi:10.1182/blood-2021-152603
  2. Lu, T, Liang J, Miao Y, et al. Epstein-Barr virus positive diffuse large B-cell lymphoma predict poor outcome, regardless of the age. Scientific Reports. 2015;5:12168. doi:10.1038/srep12168
  3. Haverkos B, Huang Y, Gru A. Frequency and clinical correlates of elevate plasma Epstein-Barr virus DNA at diagnosis in peripheral T- cell lymphomas. Int J Cancer. 2017;140(8):1899-1906. doi:10.1002/ijc.30566
  4. Dupuis J, Emile J, Mounier N, et al. Prognostic significance of Epstein-Barr virus in nodal peripheral T-Cell lymphoma, unspecified. Blood. 2006;108(13)4163-4169. doi:10.1182/blood-2006-04-017632
  5. Swerdlow SH, Campo E, Harris NL, et al. World Health Organization; 2017
  6. Mackrides N, Champman J, Larson M, et al. Prevalence, clinical characteristics and prognosis of EBV-positive follicular lymphoma. Am J Hematol. 2019;94(2):E62-E64. doi:10.1002/ajh.25357