DB107-RRV Plus DB107-FC Can Be Delivered With Radiation in Newly Diagnosed High-Grade Glioma

A multi-dose regimen of DB107-RRV (vocimagene amiretrorepvec) in combination with DB107-FC could be delivered alongside radiation, with or without temozolomide (Temodar), in patients with newly diagnosed high-grade glioma, according to an interim update of a phase 1/2 trial (NCT06504381) presented in a poster session at the 2026 SNO Annual Meeting.¹

At the October 15, 2026, data cutoff, 39 patients had consented, 32 had been dosed across 5 sites, and 28 were evaluable; 4 withdrew early for non-medical reasons. Among evaluable patients, 16 remained on study treatment; 15 had received treatment for more than 180 days, and 4 had been treated for more than 365 days, with the longest treatment duration lasting 618 days. Treatment was stopped for progression in 21% (n = 6) of evaluable patients and for other reasons in 4 patients. Additionally, 2 patients died: 1 because of febrile neutropenia that was deemed unrelated to DB107-RRV or DB107-FC, and 1 whose cause of death is under evaluation.

Among the evaluable patients, 17.9% had MGMT-unmethylated tumors (n = 5), 35.7% had low methylation (n = 10), 21.4% had medium methylation (n = 6), 21.4% had high methylation (n = 6), and 3.6% had unknown status (n = 1). The DGM7-positive genotype was reported in 12.5% of patients with an evaluable genotype (n = 24), and the investigators noted that any correlation with outcomes awaits more mature data. All 16 treated patients whose peripheral blood was tested 7 days after DB107-RRV infusion were negative for DB107-RRV RNA.

What was the design of the phase 1/2 trial of DB107-RRV plus DB107-FC in newly diagnosed HGG?

The main aim was to assess the safety and efficacy of repeated DB107-RRV dosing, delivered into the walls of the resection cavity and through the bloodstream, followed by cycles of DB107-FC alongside radiation with or without temozolomide. A secondary aim was to learn whether the DGM7 biomarker or tumor and blood transcriptomic profiles track with outcomes. Patients needed to be adults with newly diagnosed World Health Organization grade 3 or 4 glioma who had received no prior therapy, with a Karnofsky Performance Status score of at least 70, a life expectancy of at least 3 months, and adequate laboratory values. Core laboratory testing for MGMT mutations, IDH mutations, and DGM7 status took place within 4 weeks after resection.

DB107-RRV was injected into the cavity walls at surgery and infused intravenously within 8 hours. Radiation was delivered at 2 Gy per day, Monday through Friday, over 6 weeks, with DB107-FC given in weeks 1 and 2 and weeks 5 and 6; patients with MGMT-methylated tumors also received temozolomide at 75 mg/m² daily for the 6 weeks. Treatment with intravenous DB107-RRV followed on days 7 and 14, and a 4-week break preceded adjuvant therapy. Adjuvant therapy consisted of DB107-FC in 5-day courses every 28 days until progression, with temozolomide at doses of 150 mg/m² to 200 mg/m² daily for 5 days per cycle, for up to 6 cycles, in patients with temozolomide-sensitive disease. Patients with and without the DGM7 genotype were assigned 1:1 to each arm when possible.

What did earlier studies show with DB107-RRV in HGG?

DB107-RRV is a retroviral replicating vector that multiplies selectively in dividing tumor cells and carries a yeast cytosine deaminase gene. The enzyme turns DB107-FC—a prodrug of 5-fluorocytosine—into the chemotherapy 5-fluorouracil within the tumor; this conversion also clears immunosuppressive myeloid cells from the tumor microenvironment. In a phase 1 trial of 45 patients with recurrent or progressive high-grade glioma (HGG), the median overall survival was 13.6 months (95% CI, 10.8-20.0), which was improved relative to an external control (HR, 0.45; 95% CI, 0.27-0.77; P = .003).² Additionally, in the randomized phase 2/3 TOCA 5 trial (NCT02414165) of 403 patients with recurrent HGG, the median overall survival was 11.10 months with DB107-RRV plus DB107-FC (n = 201) vs 12.22 months with investigators’ choice of a single approved therapy (n = 202; HR, 1.06; 95% CI, 0.83-1.35; P = .62).³ Prespecified patient subgroup analyses of TOCA 5 showed signs of a survival benefit, and that genome-wide association analysis identified DGM7 as a potential genetic biomarker of benefit.¹

What was the safety profile of DB107-RRV plus DB107-FC alongside radiation in newly diagnosed HGG?

Through the May 19, 2026, safety cutoff, 317 adverse effect reports had been recorded. The most frequent were fatigue (15 reports; 4.73% of all reports); diarrhea (13; 4.10%); anemia (12; 3.79%); thrombocytopenia (10; 3.15%); seizure (9; 2.84%); constipation (9; 2.84%); nausea (8; 2.52%); and vomiting, neutropenia, hypokalemia, and anxiety (6 each; 1.89%). The investigators said the most common adverse effects (AEs)—fatigue, gastrointestinal symptoms, and cytopenias—were consistent with those associated with chemoradiation and with 5-fluorocytosine and 5-fluorouracil exposure.

All reported serious AEs were grade 3: pulmonary embolism (3 reports; not related to study drug), diarrhea (3; possibly related), seizures (3; not related), thromboembolic events (2; not related), pneumonia (2; 1 possibly related), nausea (2; probably related), and intracranial hemorrhage (2; not related).

What did serial MRI show in patients treated longest with DB107-RRV for HGG?

The poster displayed axial post-contrast T1-weighted MRI scans before surgery, immediately after surgery, and at the most recent on-study assessment for the 3 patients with the longest treatment: 618 days, 609 days, and 524 days, all of whom remained on study. Arrowheads marked enhancing tumor before surgery and the resection cavity afterward, and chronic bilateral subdural fluid collections, first noted after surgery, were marked in 1 of the 3 patients.

References

1. Stallard S, Kasahara N, Chen TC, et al. Clinical trial update: phase I/II study of intracranial and intravenous multi-dosing of DB107-RRV and DB107-FC in combination with radiation ± temozolomide in patients with newly diagnosed high-grade glioma. Presented at: 2026 SNO Annual Meeting; November 12-15, 2026; Philadelphia, PA. Abstract CTIM-43.
2. Cloughesy TF, Landolfi J, Hogan DJ, et al. Phase 1 trial of vocimagene amiretrorepvec and 5-fluorocytosine for recurrent high-grade glioma. Sci Transl Med. 2016;8(341):341ra75. doi:10.1126/scitranslmed.aad9784
3. Cloughesy TF, Petrecca K, Walbert T, et al. Effect of vocimagene amiretrorepvec in combination with flucytosine vs standard of care on survival following tumor resection in patients with recurrent high-grade glioma: a randomized clinical trial. JAMA Oncol. 2020;6(12):1939-1946. doi:10.1001/jamaoncol.2020.3161