Ulevostinag (STING agonist) + Pembrolizumab Scores 50% ORR in First-Line R/M HNSCC

Ulevostinag, a cyclic-dinucleotide STING agonist given intratumorally at its RP2D 540 µg, was tested with pembrolizumab 200 mg Q3W in a phase 1 dose-escalation (n = 156) and a small randomized phase 2 head-to-head in untreated recurrent/metastatic head-and-neck SCC (combo n = 8, pembro-alone n = 10). Pyrexia was the leading AE (70% in phase 1; 5 of 18 (28%) in phase 2), with 10 (6.4%) dose-limiting toxicities across all doses; no grade ≥3 immune flares reported. The combo achieved 4/8 responses (50% ORR) versus 1/10 (10%) for pembrolizumab, out-punching the ~17% ORR seen for pembro monotherapy in the KEYNOTE-048 registrational trial. Intratumoral delivery showed clear PK/PD activation of IFN-γ and CXCL10 without proportional cytokine escalation beyond 540 µg. For context, pembrolizumab + chemo typically posts ~36% ORR in this setting, so a chemo-free doublet cracking 50% is notable—though confirmation will hinge on larger cohorts.