Phase 1b/2 quemliclustat CD73 adenosine-pathway inhibitor with EV nectin-4 ADC + pembro PD‑1

Fred Hutchinson Cancer Center is running a Phase 1b/2 study adding quemliclustat (a CD73 inhibitor that aims to reduce immunosuppressive adenosine signaling in the tumor microenvironment) to the now-established backbone of enfortumab vedotin and pembrolizumab for first-line, unresectable locally advanced or metastatic urothelial carcinoma. Enfortumab vedotin (Padcev; Astellas + Seagen/Pfizer) is a nectin-4–targeted antibody–drug conjugate that delivers MMAE (a microtubule inhibitor) into tumor cells; pembrolizumab (Keytruda; Merck) is a PD‑1–blocking antibody that reinvigorates anti-tumor T cells. The trial uses an open-label dose-finding Phase 1b portion (safety/PK and recommended Phase 2 dose for quemliclustat) followed by Phase 2 expansion to estimate anti-tumor activity, with on-study imaging plus blood and optional tumor biopsies. Eligible patients have previously untreated advanced urothelial cancer arising from bladder, renal pelvis, or ureter. Clinically, EV+pembrolizumab is already a major first-line option after FDA approval, so the commercial/scientific question is whether CD73 blockade can deepen durability or increase complete responses beyond today’s standard of EV+pembro or platinum-based chemotherapy followed by maintenance avelumab in responders.