Do we understand PDAC? These tumors have a particular desmoplastic stroma, are hypovascularized, and exhibit proven high osmotic pressure in their stroma. As indicated by the 0% ORR achieved by T-DXd in 2/3+ PDACs and the lack of additive value from zolbetuximab (also an antibody), this cannot be explained solely by chemoresistance. Anti-PD-1 antibodies were also inactive.
There is no strong evidence for this, but antibodies probably cannot reach PDAC tumor cells. This is underscored by the 0% ORR to T-DXd, while some patients respond to small-molecule chemotherapy.
How can we overcome this? Potentially with next-generation small peptide compounds or direct tumor stroma remodeling.
Zolbetuximab plus gemcitabine and nab-paclitaxel in CLDN18.2+ metastatic PDAC: phase II GLEAM study
@ESMO-GI
👉Primary endpoint not met, no OS & PFS benefit
👉Toxicity manageable
🧐Not the right drug, but maybe the right target