Three years after taking QEQ278 into its first clinical trial Novartis has thrown in the towel on this unusual approach. The molecule is a fusion protein targeting NKG2D, and its study has just been marked terminated on clinicaltrials.gov, with “business decision” cited as the reason. The business decision likely relates to QEQ278’s lack of activity: the first results from this late-line solid tumour trial, presented at last October’s Triple (AACR-NCI-EORTC) meeting, showed no responses among 30 patients, half of whom experienced severe adverse events; there were two dose-limiting adverse events noted. The logic behind QEQ278 was to drive the killing of tumour cells expressing the NKG2D ligand, and to neutralise soluble NKG2D-L to resensitise NK cells. NKG2D and NKG2D-L remain popular targets for the development of cell therapies, in particular Car-NK projects, but the pipeline of protein/MAb therapeutics with this mechanism is sparse, and includes CD16A-targeting NK-cell engagers. That last modality has had problems of its own, with AbbVie, for instance, quietly terminating the Dragonfly-derived anti-NKG2D x cMet bispecific NK-cell engager ABBV-303 last year. NKG2D-targeting projects, excluding cell therapiesProjectMechanismCompanyStatusDF1001NKG2D x HER2 NK-cell engagerDragonflyPh1/2 in solid tumoursMK-4464/ DF8001NKG2D x CEACAM5 NK-cell engagerMerck & Co/ DragonflyPh1 trial +/- Keytruda completed Sep 2025QEQ278NKG2D fusion proteinNovartisPh1 trial terminated after showing 0% ORR (n=30)ABBV-303NKG2D x cMet NK-cell engagerAbbVie/ DragonflyPh1 trial +/- budigalimab terminatedDF7001NKG2D x 5T4 NK-cell engagerGilead/ DragonflyPreclinicalPBA-0091NKG2D x GARP fusion proteinPure BiologicsPreclinicalOPL-0101NKG2D x IL-2 fusion proteinValo HealthDiscontinued in preclinicalSource: OncologyPipeline.
Three years after taking QEQ278 into its first clinical trial Novartis has thrown in the towel on this unusual approach. The molecule is a fusion protein targeting NKG2D, and its study has just been marked terminated on clinicaltrials.gov, with “business decision” cited as the reason. The business decision likely relates to QEQ278’s lack of activity: the first results from this late-line solid tumour trial, presented at last October’s Triple (AACR-NCI-EORTC) meeting, showed no responses among 30 patients, half of whom experienced severe adverse events; there were two dose-limiting adverse events noted. The logic behind QEQ278 was to drive the killing of tumour cells expressing the NKG2D ligand, and to neutralise soluble NKG2D-L to resensitise NK cells. NKG2D and NKG2D-L remain popular targets for the development of cell therapies, in particular Car-NK projects, but the pipeline of protein/MAb therapeutics with this mechanism is sparse, and includes CD16A-targeting NK-cell engagers. That last modality has had problems of its own, with AbbVie, for instance, quietly terminating the Dragonfly-derived anti-NKG2D x cMet bispecific NK-cell engager ABBV-303 last year.
NKG2D-targeting projects, excluding cell therapies
