Dr Schaff on Safety and OS Outcomes With L19TNF Plus Lomustine in Recurrent Glioblastoma

“There didn’t seem to be a difference [in] AEs [between] the different arms, so [the combinations studied in] all 6 arms were thought to be safe and well tolerated.”

Lauren Schaff, MD, a neurologist and neuro-oncologist and associate director of the Neuro-Oncology Fellowship Program at Memorial Sloan Kettering Cancer Center, discussed results from the phase 2 GLIOSTELLA trial (NCT06336291) evaluating the immunocytokine L19TNF (onfekafusp alfa) in combination with lomustine in patients with recurrent glioblastoma.

Notably, these findings were presented at the 2026 SNO Annual Meeting.

L19TNF is a fusion of tumor necrosis factor and the L19 antibody, which targets the extra-domain B of fibronectin, an antigen expressed in glioblastoma. The trial enrolled 90 patients, 86 of whom were treated, and assessed 2 lomustine doses (90 mg/m² and 110 mg/m²) combined with 3 L19TNF doses (7 µg/kg, 10 µg/kg, and 13 µg/kg), across 6 arms in total, Schaff explained.

The primary end point was safety, Schaff said. The most common adverse effect was elevated liver enzyme levels, which were easily reversible; these usually recovered within 48 hours. Infusion reactions related to L19TNF were also observed, which was not surprising, she noted. There were no grade 5 adverse effects (AEs), and no apparent differences in AEs across arms.

A key efficacy end point was the overall survival rate at 12 months, which was 42% in this pretreated population. Additionally, the median overall survival (OS) was 10.6 months (95% CI, 8.2-12.8), Schaff said. The median OS values ranged from 8.8 months to 13.4 months across dose levels, with no obvious differences between the arms.

Schaff cited limitations of this trial, including that this was not an efficacy study and had no control arm. In addition, measurable disease was not required for enrollment, she explained. Since some patients enrolled on the trial after surgery and might not have had detectable glioblastoma on MRI, there are questions about drug penetrance in those patients, Schaff said.

As a next step, L19TNF is being evaluated in the upfront setting in a European study in combination with radiation and temozolomide (Temodar), Schaff noted. She said the hope is to take the agent into a larger trial after seeing those results.