TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint Inhibitor-Na?ve Locally Advanced or Metastatic Urothelial Carcinoma

We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint inhibitor-na & iuml;ve patients with locally advanced/metastatic urothelial carcinoma (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 of subsequent cycles in 21-day cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month progression-free rates were 46.4% and 36.5%, respectively. Median OS was not reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, respectively. In post hoc analysis, patients with a tumor infiltrating CD8(+) lymphocyte (CD8(+) TIL) count >= 99 and/or programmed cell death ligand 1 (PD-L1) combined positive score (CPS) >= 50 and lymphocyte count >1,380 cells/mu L had higher ORRs and prolonged PFS versus patients with a CD8(+) TIL count <99, PD-L1 CPS <50, and lymphocyte count <= 1,380 cells/mu L. Thirty-four (94.4%) patients receiving combination therapy experienced treatment-related adverse events (AE), with pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade >= 3 treatment-related AEs occurred in >= 10% of patients. TAS0313 plus pembrolizumab combination therapy showed promising efficacy and manageable safety in la/mUC.