THINK Disappoints in High-Risk MDS and AML Patients

NKG2D is an activating receptor capable of binding eight ligands overexpressed in AML/MDS. The THINK study evaluated CYAD-01 with no preconditioning, and the DEPLETHINK study trialed CYAD-01 with cyclophosphamide and fludarabine preconditioning.

In this video, David S. Sallman, MD, of Moffitt Cancer Center in Tampa, Florida, shares outcomes from the two early-stage clinical studies, which he presented at December’s American Society of Hematology (ASH) virtual meeting.

Following is a transcript of his remarks:

At ASH 2020, we were excited to present phase I clinical trials of CYAD-01, which is a first-generation NKG2D CAR T-cell product in high-risk MDS and AML patients. Two protocols were implemented to study this CAR, one it uses no lymphodepletion where patients get infusions of cells every two weeks and can get up to six infusions (THINK trial). We then looked at the importance of lymphodepletion in the DEPLETHINK trial, where patients get standard fludarabine/cyclophosphamide followed by infusion, and then can get the option of consolidation.

We use a novel process called “OptimAb” to generate a more optimal T-cell product. Although unfortunately, really this did not significantly improve activity. We did see several patients that had some clinical benefit, as well as one patient who had a marrow response as well as was ultimately bridge to transplant, and had a remission now for over three years. Importantly, with the addition of lymphodepletion we did not overall see improved response rates.

And really thus in conclusion, although the product has been safe, and we do see clinical activity, I really believe the next steps to further enhance activity are with a next generation product, which will also be presented at ASH via poster 990 (CYCLE-1 trial), where we actually knock out MICA and MICB in the product to ideally improve persistence expansion and overall efficacy with some early data support that.