On August 8, 2023 Viracta Therapeutics, Inc. (Nasdaq: VIRX), a clinical-stage precision oncology company focused on the treatment and prevention of virus-associated cancers that impact patients worldwide, reported the publication of clinical data from an open-label, multicenter, Phase 1b/2 study of Nana-val in 55 patients with R/R EBV+ lymphoma in Blood Advances. Results showed complete responses (CRs) achieved and ongoing durable responses observed out to approximately 36 months across multiple EBV+ lymphoma subtypes, including some of the most aggressive cancers: peripheral T-cell lymphoma (PTCL), diffuse large B-cell lymphoma (DLBCL), and post-transplant lymphoproliferative disease (PTLD) (Press release, Viracta Therapeutics, AUG 8, 2023, View Source [SID1234633996]). This paper titled, "Targeted therapy with nanatinostat and valganciclovir in recurrent Epstein-Barr virus-positive lymphoid malignancies: a Phase 1b/2 study," can be found here.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"Results from both retrospective and prospective clinical studies link EBV-positivity to significantly inferior survival in multiple lymphoma subtypes, highlighting the pressing need for novel therapies for this underserved patient population," said Pierluigi Porcu, M.D., Professor of Medical Oncology, Director of the Division of Hematologic Malignancies and Hematopoietic Stem Cell Transplantation, Department of Medical Oncology at Thomas Jefferson University, and corresponding author on the paper. "The newly published Phase 1b/2 study data showcase the potential of Viracta’s innovative ‘Kick and Kill’ approach to effectively address this need, with results demonstrating Nana-val’s favorable safety and tolerability profile and promising durable signal of efficacy in heavily pre-treated patients. These data served as a catalyst for the advancement of Nana-val into the confirmatory NAVAL-1 trial, which has an elegant multi-stage design to potentially support registration."

Darrel P. Cohen, M.D., Ph.D., Viracta’s newly appointed Chief Medical Officer added, "Having these Phase 1b/2 clinical trial data peer-reviewed and published in such a prestigious journal of the American Society of Hematology (ASH) (Free ASH Whitepaper) provides important external validation for Nana-val’s therapeutic potential. The substantial number, depth, and durability of Nana-val’s clinical responses with a favorable safety profile observed in this heavily pre-treated EBV-positive lymphoma patient population are impressive, several of which are still ongoing. This publication further supports the recently announced expansion of the NAVAL-1 trial’s EBV-positive peripheral T-cell lymphoma cohort, representing an exciting time for our clinical trial program, and we look forward to providing more updates on its progress in the future."

Data published from the study showed that CRs were achieved across multiple EBV+ lymphoma subtypes, with a reported overall response rate (ORR)/CR rate of 40%/19% in 43 evaluable patients. In patients with EBV+ PTCL, which was recently established as the leading indication in Viracta’s pivotal NAVAL-1 trial, ORR/CR rates of 67%/50% were reported (n=6 including both EBV+ PTCL-not otherwise specified [PTCL-NOS] and angioimmunoblastic T-cell lymphoma [AITL] patients). Of note, one of the CRs was achieved in a patient whose disease never responded to second-line histone deacetylase inhibitor (HDACi) treatment. In 6 patients with EBV+ DLBCL, a rare aggressive and distinct B-cell lymphoma subtype characterized by an adverse clinical outcome, ORR/CR rates of 67%/33% were reported. Of note, one of the CRs was achieved in a patient whose disease never responded to first-line R-CHOP chemotherapy.

The published paper includes an additional 10-month follow-up period, which demonstrated durable response durations across multiple EBV+ lymphoma subtypes. As of the expanded data cutoff date of September 1, 2022, multiple patients remained in an ongoing durable response in excess of 30 months, with two patients in an ongoing response of approximately 36 months. The median time to response was 1.8 months, and the median duration of response was approximately 10 months in a heavily pre-treated patient population. Overall, trial participants received a median of two prior therapies before entering the trial, with 75% (41/55) being refractory to their last therapy.

Data also showed that all-oral Nana-val was well tolerated with reversible low-grade AEs. The most commonly observed treatment-emergent AEs were reversible cytopenias, low-grade creatinine elevations, and gastrointestinal symptoms. Initial data from the Nana-val Phase 1b/2 clinical trial were previously presented at the 2021 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

About Nana-val (Nanatinostat and Valganciclovir)
Nanatinostat is an orally available HDACi 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. Ongoing clinical trials include a pivotal, global, multicenter, open-label Phase 2 basket trial in multiple subtypes of relapsed or refractory EBV+ lymphoma (NAVAL-1) as well as in combination with pembrolizumab in a multinational Phase 1b/2 trial in patients with recurrent or metastatic EBV+ nasopharyngeal carcinoma and other EBV+ solid tumors.

About EBV-Associated Cancers
Approximately 90% of the world’s adult population is infected with 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.