Phase Ib study of anti-PD-L1 monoclonal antibody socazolimab in combination with nab-paclitaxel as first-line therapy for advanced urothelial carcinoma.

person Rong Duan Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China info_outline Rong Duan, Yixun Liu, Xuechun Hu, Chuanliang Cui, Lu Si, Xinan Sheng, Zhi Liu, Ping Xiang, Xieqiao Yan, Siming Li, Li Zhou, Juan Li, Yu Jie Li, Rachel Ng, Xiang Rong Dai, Benjamin Xiaoyi Li, Zhihong Chi, Jun Xiao, Jun Guo, Bixia Tang

Authors person Rong Duan Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China info_outline Rong Duan, Yixun Liu, Xuechun Hu, Chuanliang Cui, Lu Si, Xinan Sheng, Zhi Liu, Ping Xiang, Xieqiao Yan, Siming Li, Li Zhou, Juan Li, Yu Jie Li, Rachel Ng, Xiang Rong Dai, Benjamin Xiaoyi Li, Zhihong Chi, Jun Xiao, Jun Guo, Bixia Tang Organizations Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China, The First Affiliated Hospital of USTC (Anhui Provincial Hospital), He Fei, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma Oncology, Beijing Cancer Hospital, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China, Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology,Peking University Cancer Hospital & Institute, Beijing, China, Lee's Pharmaceutical Holdings Limited, Hong Kong, China, Lee's Pharmaceutical Holdings Ltd, Hong Kong, China, The First Affiliated Hospital of USTC, Anhui Provincial Hospital, Hefei, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma & Sarcoma,Peking University Cancer Hospital & Institute, Beijing, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: PD-1/PD-L1 immune checkpoint inhibitors (ICIs)0have demonstrated activity in the postplatinum and platinum-ineligible settings for advanced urothelial carcinoma (aUC). As only around 30% of patients with aUC can tolerate platinum standard treatment, first-line ICIs combined with non-platinum drugs have certain research value. Therefore we assessed the safety and efficacy of anti-PD-L1 monoclonal antibody Socazolimab in combination with nab-paclitaxel as first line therapy in aUC (NCT04603846). Methods: This is a multi-center,single-arm, phase Ib study which enrolled aUC patients with treatment-naive or first recurrence more than 6 months after the end of adjuvant chemotherapy in China. Eligible patients received Socazolimab (5mg/kg) and nab-paclitaxel (260mg/m 2 ) every 3 weeks. Primary endpoint was to investigate the safety and tolerability of nab-paclitaxel in combination with Socazolimab. Second endpoints were the objective response rate (ORR) and progression-free survival (PFS). Results: 20 patients were enrolled, including 5 renal pelvis urothelial carcinoma, 8 bladder urothelial carcinoma, and 7 ureteral carcinoma. The median age was 69 years. As of January 14, 2022, the median follow-up time was 5.49 months. Median number of treatment cycles was 6.5 cycles. No patients had dose limiting toxicity. Among the 17 patients who had received at least one tumor assessment, 8 patients achieved partial responses. ORR was 52.94% (95% CI, 27.81-77.02). DCR was 88.24% (95% CI, 63.56-98.54). Median PFS was 8.18 months (95% CI, 5.32-13.60). Adverse reactions related to the study drug were mainly Grade 1-2. Common adverse reactions included rash (6/20,30%), increased alanine aminotransferase (6/20, 30%), increased γ-glutamyltransferase (4/20, 20%),sinus bradycardia (4/20, 20%), increased aspartate aminotransferase (4/20, 20%),pruritus (3/20, 15%). Grade 3 or higher treatment-related adverse events occurred in 4 (20%) patients, mainly Grade 3 increases in alanine aminotransferase (2/20, 10%). No confirmed treatment-related deaths occurred, and no treatment-related deaths occurred, and no new safety signals were observed. Conclusions: Socazolimab combined with nab-paclitaxel as first-line treatment was effective and well-tolerated in Chinese patients with advanced urothelial carcinoma, warranting phase II trials. Clinical trial information: NCT04603846.