Dr Olson on Data With the PRAME-Targeted ImmTAC Brenetafusp in Advanced Melanoma

“The takeaways [are] the survival and the disease control rate, which is over 50%...These intermediate end points don’t reflect the overall benefit of these therapies, so that’s what’s interesting and exciting.”

Daniel Olson, MD, assistant professor of medicine at UChicago Medicine, discussed the durable disease control observed with the T-cell receptor bispecific ImmTAC brenetafusp in a phase 1/2 trial (NCT04262466) in patients with advanced melanoma.

Previously reported data from the study demonstrated that brenetafusp monotherapy was tolerable and had robust T-cell activation which translated to encouraging clinical activity in solid tumors, including heavily pretreated cutaneous melanoma. In updated phase 1 findings, which were presented at the 2026 ASCO Annual Meeting, the objective response rate with the single agent was 6% at the 40-mcg dose and 17% at the 160-mcg dose. Median progression-free survival was approximately 4 months, but medians don’t fully capture the clinical benefit observed with this agent, Olson stressed. The disease control rate was 52%—56% at the 40 mcg-dose level and 67% at the 160 mcg-dose level, and the median overall survival was 14.3 months (95% CI, 11.3-20.4).

This pattern mirrors what has been observed with other ImmTAC therapies such as tebentafusp (Kimmtrak), Olson noted. On the safety side, the unique phenomenon of tachyphylaxis, which is characterized by cytokine release syndrome (CRS) at initial doses, was observed, with grade 1/2 CRS occurring at rates of 56% and 42% at the 40-mcg and 160-mcg doses, respectively. This is consistent with the broader class effect seen with T-cell engagers, Olson noted. A step-up dosing approach was employed to manage early CRS, which requires close monitoring upfront. However, once patients reach a stable dose, tolerability is generally favorable, with CRS attenuating over time.

These phase 1 data support the ongoing phase 3 PRISM-MEL trial (NCT06112314) evaluating the combination of brenetafusp and nivolumab (Opdivo) vs standard nivolumab-based regimens in the frontline setting. Because the mechanism is distinct from immune checkpoint inhibition, the combination may offer additive benefit, potentially reaching patients who do not respond to PD-1/PD-L1 blockade alone.