Combination of a PD-1/CTLA-4 bispecific antibody with orally active PD-L1 inhibitor MAX-10181 effectively increased the percentage of tumors inhibited in animal model study

Abstract The key players in the current immuno checkpoint inhibition (ICI) treatment are antibodies or bispecific antibodies targeting PD-1. PD-L1 or CTLA-4. While these drugs provided a small number of patients with tumor shrinking (ORR between 10-30%) as a single agent, they did not lead to desirable treatment survival as measured by OS/PFS. Many combination studies are in progress in both preclinical and clinical settings to find an effective way to achieve prolonged OS/PFS in ICI treatment. Herein, we would like to report our most recent findings of combination of a PD-1/CTLA-4 bispecific antibody with our orally active, clinical stage PD-L1 inhibitor MAX-10181 in animal model study. The key observations are as follow: •The PD-1/CTLA-4 bispecific antibody group (n=10, average starting tumor volume= 68 mm3) demonstrated (a) 2 tumors (20%) in the slow volume shrinking mode with volume between 60-20 mm3, and (b) 4 tumors (40%) in the fast volume growing mode with volume above 500 mm3 •The combination group (n=10, average starting tumor volume= 68 mm3) demonstrated (a) 2 tumors (20%) in the fast volume shrinking mode with volume less than 20 mm3, (b) 1 tumor (10%) in the slow volume shrinking mode with volume between 60-20 mm3, and (c) only 1 tumor (10%) in the fast volume growing mode with volume above 500 mm3 These results indicate the potential of prolonged OS/PFS to combine PD-1/CTLA-4 bispecific antibody with orally active, small molecule MAX-10181 which recently completed Phase I trial. We will present the full study results in the coming AACR meeting. Citation Format: Yuguang Wang, Yuan Gao, Chenyu Mao, Nong Xu, Qiang Zhang, Jing Wang, Zhenhua Feng, Yonghong Zhu, Zhongmin Wang, Baiyong Li. Combination of a PD-1/CTLA-4 bispecific antibody with orally active PD-L1 inhibitor MAX-10181 effectively increased the percentage of tumors inhibited in animal model study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB098.