Final results of a phase 2 study of HDACi chidamide and PD-1 inhibitor for advanced urothelial carcinoma after platinum therapy.

4563 Background: Epigenetic dysregulation is commonly correlated with the pathogenesis and development in urothelial carcinoma. The preliminary results demonstrated that the combination of chidamide (CHI) and tislelizumab (TIS) was well tolerated with clinically meaningful activity in patients (pts) with advanced or metastatic urothelial carcinoma (mUC). Confirmed ORR was 41.7%, median PFS was 4.6 months. Here we present results from the final analysis. Methods: Eligible pts aged 18 to 75 years old had recurrend or progressed after platinum-based chemotherapy to assess the efficacy and safety of CHI and PD-1 inhibitor in mUC. All pts received 30 mg oral CHI twice weekly in combination with TIS 200mg Q3W, until progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). The secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS) , and safety. Results: From Jan. 2021 to Oct. 2023, a total of 45 pts were enrolled at Sun Yat-sen University Cancer center. At the data cut-off (Aug, 2024), the median duration of follow-up was 23.2 months (95%CI: 17.2-31.9). Median age was 63 years (IQR: 57-68). ORR and DCR were 44.4% (12CR, 8PR; 95%CI, 29.6-60.0%) and 60% (27/45; 95%CI, 44.3-74.3%), respectively. Median duration of response (DOR) was not evaluable (95%CI, 8.8-NE). Median PFS and OS were 7.0 months (95%CI, 2.4-10.3) and 20.3 months (95%CI, 10.7-NE), respectively. The most common treatment emergent adverse events (TEAEs) included anemia, anorexia, thrombocytopenia, neutropenia, leukopenia, fatigue, hypoalbuminemia. Grade 3 or above TEAEs (≥10%) were neutropenia 24.4%, thrombocytopenia 20.0%, anemia 13.3%.No pts died due to an adverse event attributed to study trearment. Conclusions: This study is the first trial to show that combining HDAC inhibitor with PD-1 antibody is a feasible and efficacious novel approach in mUC. Chidamide plus tislelizumab could be a new treatment option in this patient population. Clinical trial information: NCT04562311 . CHI+TIS (n=45) ORR (95% CI), % 44.4 (29.6- 60.0) CR, % 26.7% (12/45) PFS Median (95% CI), mo36-mo rate (95% CI), % 7.0 (2.4-10.3)26.3 (13.4-41.1) OS Median (95% CI), mo36-mo rate (95% CI), % 20.3 (10.7-NE)45.9 (28.8-61.4) DOR Median (95% CI), mo NE (8.8-NE)