Oral molecular glue degrader with or without spartalizumab shows immune activation and tumour control in solid tumours

Dr Elena Garralda speaks to ecancer about the early-phase results of DKY709, an oral molecular glue degrader targeting IKZF2 in regulatory T cells, evaluated alone and in combination with the anti–PD-1 antibody spartalizumab in patients with advanced solid tumours.

DKY709 achieved robust degradation of IKZF2, indicating effective modulation of immune-suppressive regulatory T cells.

Clinically, both monotherapy and combination therapy demonstrated meaningful disease control and tumour reductions in heavily pretreated patients, including those with melanoma, non-small cell lung cancer, and nasopharyngeal carcinoma.

The safety profile was manageable, with common adverse events including muscle-related symptoms, liver enzyme elevations, and reversible peripheral neuropathy, which was reduced with optimised dosing schedules.

Dr Garralda highlights that these findings support DKY709 as a novel immunomodulatory approach with potential to enhance antitumor immune responses, both alone and in combination with checkpoint inhibition.