On November 30, 2022 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported preliminary dose-ranging data from the first two dose levels of the dose escalation part of the Phase 1b/2 study of Nana-val in patients with EBV+ recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) (Press release, Viracta Therapeutics, NOV 30, 2022, View Source [SID1234624620]). The data are featured in an abstract accepted for a poster presentation at the European Society for Medical Oncology Immuno-Oncology Congress (ESMO-IO), which is taking place both virtually and in-person at the Palexpo Exhibition Centre in Geneva, Switzerland, from December 7 – 9, 2022.

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The Phase 1b/2 trial’s first two dose levels enrolled seven patients with EBV+ R/M NPC, six of whom were evaluable for response as of the abstract’s data cut-off date (September 15, 2022). At the time of enrollment, patients had received a median of two prior systemic therapies. All patients were refractory to their last therapy with bone (6/7), liver (5/7), and lung (3/7) metastases.

Key data reported in the abstract include:

Nana-val was well tolerated with no dose limiting toxicities (DLTs) reported. Most common Grade 1-2 AEs were fatigue, nausea, and increased creatinine (n=3 each).
Two of six evaluable patients achieved stable disease (SD) per RECIST v1.1 criteria.
Plasma EBV DNA titers decreased or remained stable in both patients achieving SD, while rising in patients with progressive disease.
"We initiated this study earlier this year, and this abstract reports the first preliminary data on our all-oral combination regimen in patients with advanced Epstein-Barr virus-positive NPC, where few treatment options are available," said Lisa Rojkjaer, M.D., Chief Medical Officer of Viracta. "Starting with the recommended Phase 2 dose from our Phase 1b/2 study in lymphoma, the combination of nanatinostat and valganciclovir was thus far well-tolerated in the initial dose escalation cohorts, with no DLTs reported. Dose escalation continues as we evaluate optimizing the use of both agents in the solid tumor setting. We look forward to the advancement of this study to determine the recommended Phase 2 dose."

As previously reported, the Phase 1b/2 trial is currently progressing through its third dose escalation cohort, with enrollment in the third dose level completed. Further safety data from the third dose level will be presented in the abstract’s corresponding poster at ESMO (Free ESMO Whitepaper)-IO. Viracta recently amended the trial protocol to include additional dose levels in the Phase 1b dose escalation portion, which is designed to determine the optimal recommended Phase 2 dose (RP2D). The company anticipates initiating the Phase 2 randomized expansion portion of the Phase 1b/2 trial in the second half of 2023.

Additional details related to the abstract and upcoming poster, entitled, A Phase 1b/2 Study of Nanatinostat (Nstat) Plus Valganciclovir (VGCV) in Advanced Epstein-Barr Virus Positive (EBV+) Solid Tumors and with Pembrolizumab (PEM) in Recurrent/Metastatic Nasopharyngeal Carcinoma (R/M NPC), are shown below.

Presentation Number: 156P
Poster Session Date: December 8, 2022
Poster Session Time: 12:30 p.m. CET

The abstract is currently available for viewing on the congress website. A copy of the poster will be available on the "Events and Webcasts" section of the Viracta website following the conclusion of the congress.

About the Phase 1b/2 Trial of Nana-val in EBV+ R/M NPC and Other EBV+ Solid Tumors
This Phase 1b/2 trial (NCT05166577) is an open-label, multinational trial evaluating Nana-val alone and in combination with pembrolizumab. The Phase 1b dose escalation portion is designed to evaluate safety and to determine the recommended Phase 2 dose (RP2D) of Nana-val in patients with EBV+ RM-NPC. In Phase 2, up to sixty patients with EBV+ RM-NPC will be randomized to receive Nana-val at the RP2D with or without pembrolizumab to evaluate safety, overall response rate, and potential pharmacodynamic markers. Additionally, patients with other advanced EBV+ solid tumors will be enrolled to receive Nana-val at the RP2D in a Phase 1b dose expansion cohort.

About Nana-val (Nanatinostat and Valganciclovir)

Nanatinostat is an orally available histone deacetylase (HDAC) inhibitor being developed by Viracta. Nanatinostat is selective for specific isoforms of Class I HDACs, which are key to inducing viral genes that are epigenetically silenced in Epstein-Barr virus (EBV)-associated malignancies. Nanatinostat is currently being investigated in combination with the antiviral agent valganciclovir as an all-oral combination therapy, Nana-val, in various subtypes of EBV-associated malignancies.

About EBV-Associated Cancers

Approximately 90% of the world’s adult population is infected with Epstein-Barr virus (EBV). Infections are commonly asymptomatic or associated with mononucleosis. Following infection, the virus remains latent in a small subset of cells for the duration of the patient’s life. Cells containing latent virus are increasingly susceptible to malignant transformation. Patients who are immunocompromised are at an increased risk of developing EBV+ lymphomas. EBV is estimated to be associated with approximately 2% of the global cancer burden including lymphoma, nasopharyngeal carcinoma and gastric cancer.