First Patient With Epstein-Barr Virus-Positive NPC Dosed in Phase 1b/2 Trial of Nana-val

The first patient with Epstein-Barr virus (EBV)–positive recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) has received the oral combination nanatinostat and valganciclovir (Nana-val) in a multinational, phase 1b/2 trial (NCT05166577), according to a news release from the developer, Viracta Therapeutics, Inc.¹

This study will evaluate the preliminary efficacy and safety of Nana-val in patients with (EBV)–positive R/M NPC and other advanced EBV–positive solid tumors. Nana-val will be tested alone and in combination with pembrolizumab (Keytruda).¹

This is an open-label trial that aims to evaluate safety and efficacy. The phase 1b portion of the trial will evaluate safety and look to find the recommended dose for phase 2. Phase 2 of the trial will randomize up to 60 patients with EBV–positive R/M NPC to receive the Nana-val phase 2 recommended dose alone or paired with pembrolizumab. Phase 2 will evaluate safety, overall response rate (ORR), and potential pharmacodynamic markers. Additional patients with EBV–positive solid tumors will be enrolled in phase 1b expansion cohort to receive the recommended dose of Nana-val.

"The initiation of dosing in this clinical trial represents an important milestone for Viracta and is a critical step in potentially expanding the clinical applicability of the targeted all-oral Nana-val combination beyond lymphoma," said Lisa Rojkjaer, MD, chief medical officer of Viracta, in a press release.

Another trial that includes this oral combination is the phase 1/2 study (NCT03397706), which was presented at the 62nd American Society of Hematology Annual Meeting. This specific trial observed Nana-val in treating patients with relapsed/refractory (R/R) EBV–positive lymphomas.

This trial showed a favorable safety profile and encouraging efficacy data for the Nana-val combination. The overall response rate was 80% (8/10) and complete response rate (CR) was 40% (4/10) in patients with T/NK-cell non-Hodgkin lymphoma. In patients with diffuse large B-cell lymphoma, the ORR was 66% (4/6) and CR was 33% (2/6). The median duration of response was 10.4 months.²

Most treatment-related adverse events (TRAEs) were mild. The most common TRAEs were thrombocytopenia (33%), nausea (29%), neutropenia (26%), and fatigue (24%). The most common grade 3/4 TRAEs (in ≥5% of patients) were neutropenia (14%), anemia (9%), and nausea (9%). Most grade 3/4 toxicities were reversible cytopenias with limited extra-hematologic toxicity.^2,3

Rojkjaer continued, "Advanced NPC patients have poor outcomes and are in urgent need of effective treatment options. We are looking forward to evaluating the clinical profile of this novel combination therapy and exploring potential synergies with a PD-1 inhibitor.”

_References

_{1. Viracta Therapeutics Announces Presentation of Updated Phase 2 Data at ASH 2020 and Productive Outcome of its Recent End of Phase 2 Meeting with the FDA. Press Release. Viracta Therapeutics. January 31, 2022. Accessed January 31, 2022. https://bit.ly/3Hg55xK}

_{2. Viracta Therapeutics Announces Presentation of Updated Phase 2 Data at ASH 2020 and Productive Outcome of its Recent End of Phase 2 Meeting with the FDA. Press Release. Viracta Therapeutics. December 7, 2020. Accessed January 31, 2022. https://prn.to/3IS4wdL}

_{3. Porcu P, Haverkos B, Alpdogan O, et al. Oral nanatinostat (Nstat) and valganciclovir (VGCV) in patients with recurrent epstein-barr virus (EBV)-positive lymphomas: initial phase 2 results. Presented at the 62nd American Society of Hematology Annual Meeting; December 2-5, 2020. Accessed January 31, 2022. https://bit.ly/3ocErOM}