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Receives Fast Track Designation for Nanatinostat Combo for Treatment of EBV-Associated Lymphomas
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for nanatinostat in combination with valganciclovir for the treatment
of relapsed/refractory Epstein-Barr virus (EBV)-positive lymphoid malignancies.
Phase 1b/2 clinical study evaluates three doses of the combination of nanatinostat with an antiviral valganciclovir for the treatment of EBV-associated cancers. Both drugs are taken orally and can be given on an out-patient basis.
• Responses were observed across all doses, and in B- and T-cell subtypes, including Hodgkin's Lymphoma.
• The overall objective response rate (ORR) of 58%, complete response rate (CRR) of 33%, and disease stabilization rate (DSR) of 75% is encouraging, and warrants advancement to the Phase 2 stage of
• The combination was well-tolerated and the most common adverse events were hematologic, easily managed, and resolved without sequalae or bleeding events.
• A cohort evaluating intermittent dosing of nanatinostat (4 days on and 3 days off) in combination with daily valganciclovir is being evaluated as the recommended Phase 2 dose.
"This highlights the potential of our proprietary Kick and Kill therapeutic approach to treat a wide range
of EBV positive cancer patients, with responses seen across all doses in both T cell and B cell lymphomas in our ongoing Phase 1b/2 study,” said Ivor Royston, MD, Viracta’s CEO. “Targeting the EBV virus to treat cancer is an elegant epigenetic approach that
may modify the interaction between the virus and the tumor microenvironment, while stimulating the immune response. This approach, while in the early stages of research, has now proven successful, with promising results demonstrated with nanatinostat and valganciclovir
Nanatinostat (VRx-3996) is an orally available histone deacetylase (HDAC) inhibitor. Nanatinostat is selective for specific isoforms of Class 1 HDACs which is key to inducing latent viral genes in
EBV-associated malignancies. The nanatinostat and valganciclovir combination is being investigated in EBV-associated lymphomas in an ongoing Phase 2 clinical trial [NCT03397706]. Currently, there are no approved treatments for EBV-associated lymphomas that
specifically target the virus.
Fast Track is one of the expedited programs offered by the FDA to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life-threatening
condition. Fast track designation is intended to facilitate development and expedite review of drugs to treat serious and life-threatening conditions so that an approved product can reach the market expeditiously.
Therapeutics and Alligator Bioscience Reveal New Preclinical Data for ALG.APV-527
Preclinical data show that ALG.APV-527 is well tolerated with repeated dosing .
ALG.APV-527 is a novel immunotherapeutic candidate intended for the treatment of a variety of 5T4-positive solid tumors. It is designed to induce signaling through
the co-stimulatory receptor 4-1BB (CD137), which is present on activated cytotoxic T cells and natural killer (NK) cells. Once activated, it is designed to promote potent and selective tumor-directed immune activation in the presence of the tumor associated
antigen, 5T4, which is present on many different types of solid tumors.
Prelim in vivo data show it has potent anti-tumor activity and induces an immunological memory response and the preclinical data presented at SITC show that ALG.APV-527
selectively enhances T cell and NK cell responses in the presence of 5T4 in vitro and displays potent and sustained tumor suppression in vivo.
The preclinical studies demonstrate that ALG.APV-527:
• Enhances CD8+ T cell and NK function and proliferation preferentially over that of CD4+ T cells, upon 5T4-mediated crosslinking
• In preliminary in vivo studies in a human 4-1BB knock in model, induces rejection of established murine bladder cancer cells expressing human 5T4 at doses of 20 µg in mice and induces anti-tumor
immunological memory responses
• Is well tolerated after repeated dosing in a GLP toxicology study above the expected human dose and displays an antibody-like half-life of up to 9.5 days.
"We're pleased that ALG.APV-527 continues to show promising preclinical results. The preclinical data strongly support a potent effect of ALG.APV-527 without compromising on safety. The ability of
ALG.APV-527 to induce potent anti-tumor T cell and NK cell activity suggests 4-1BB is an attractive target for designing new immuno-oncology therapeutics. Monospecific 4-1BB-directed antibodies have been challenged by dose-limiting liver toxicities. As a
novel bispecific antibody ALG.APV-527 may circumvent these challenges and minimize systemic toxicity by stimulating 4-1BB function only when co-engaged with the tumor antigen, 5T4" said Jane Gross, Ph.D., Chief Scientific Officer for Aptevo.
Image credits: San Antonio Postcard licensed under Creative Commons BY-NC-ND; Epstein-Barr Virus &
Stained Solid Tumor images licensed under Creative Commons BY-SA
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