A phase 1/2 trial evaluating IDE397, a MAT2A inhibitor, combined with sacituzumab govitecan-hziy (Trodelvy) shows encouraging activity in late-line MTAP-deletion urothelial cancer.
Two expansion cohorts were assessed. Dose Level 1 (IDE397 15 mg + Trodelvy 10 mg/kg, n=9) achieved a 33% objective response rate (ORR) and 100% disease control rate (DCR). Dose Level 2 (IDE397 30 mg + Trodelvy 7.5 mg/kg, n=7) showed a higher ORR of 57% and DCR of 71%, exceeding historical outcomes with Trodelvy alone.
The combination was generally well tolerated. Dose Level 2 reported no serious treatment-related adverse events; Grade ≥3 toxicities included anemia, asthenia, and diarrhea. Patients enrolled had advanced or metastatic solid tumors with homozygous MTAP loss and prior therapy failure. The trial is now extending to other cancers, including NSCLC, building on prior IDE397 monotherapy data showing a 33% confirmed response rate in MTAP-deleted tumors.