Phase Ib/IIa safety and efficacy of PM8002, a bispecific antibody targeting PD-L1 and VEGF-A, as a monotherapy in patients with advanced solid tumors.

person Ye Guo Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China info_outline Ye Guo, Jun Guo, Ying Cheng, Zhen Wang, Yongsheng Li, Dongqing Lv, Yongmei Yin, Guiling Li, Lingying Wu, Yi Huang, Shuqing Wei, Lin Shen, Huaxin Duan, Jiuwei Cui, Hong Luo, Xiumin Li, Kejun Nan, Chunyan Wang, Su-xia Luo, Ruonan Liu

Authors person Ye Guo Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China info_outline Ye Guo, Jun Guo, Ying Cheng, Zhen Wang, Yongsheng Li, Dongqing Lv, Yongmei Yin, Guiling Li, Lingying Wu, Yi Huang, Shuqing Wei, Lin Shen, Huaxin Duan, Jiuwei Cui, Hong Luo, Xiumin Li, Kejun Nan, Chunyan Wang, Su-xia Luo, Ruonan Liu Organizations Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China, Department of Oncology, Jilin Cancer Hospital, Changchun, China, Linyi Cancer Hospital, Linyi, China, Department of Medical Oncology, Chongqing University Cancer Hospital, Chongqing, China, Taizhou Hospital of Zhejiang Province, Taizhou, China, Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China, Union Hospital Tongji Medical College Huazhong University of Science and Technology, Wuhan, China, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China, Hubei Cancer Hospital, Hubei, China, Shanxi Provincial Cancer Hospital, Taiyuan, China, Peking University Cancer Hospital & Institute, Beijing, China, Hunan Provincial People's Hospital, Changsha, China, First Hospital of Jilin University, Changchun, China, Chongqing University Cancer Hospital, Chongqing, China, Linyi Cancer Hospital, Shandong, China, Xi 'an International Medical Center Hospital, Xian, China, Liaoning Cancer Hospital & Institute, Shenyang, China, Henan Cancer Hospital, Zhengzhou, China Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Biotheus Inc Background: PM8002 is a bispecific antibody targeting both PD-L1 and VEGF-A. We had completed dose escalation from 1mg/kg to 45mg/kg and had not found DLT/MTD. In a Phase Ib dose expansion and Phase IIa studies we are evaluating the safety and preliminary anti-tumor activity of PM8002 as a monotherapy. Here, we provide an update of PM8002 Phase Ib/IIa results. Methods: During Phase Ib dose-expansion and Phase IIa studies, the majority of patients received PM8002 at 20mg/kg Q2W or 30mg/kg Q3W as a monotherapy (recommended phase II doses). The primary endpoint was ORR with secondary endpoints/objectives including safety. Results: As of Feb 3, 2023, 263 patients of advanced solid tumor with prior 0 to 4 line systematic treatment had been enrolled (1mg/kg Q2W [n=1], 10mg/kg Q2W [n =1], 20mg/kg Q2W [n=190], 20mg/kg Q3W [n=4], 30mg/kg Q2W [n=4], 30mg/kg Q3W [n=52], and 45mg/kg Q3W [n=11]). The median duration of exposure was 10.6 weeks (range, 0.1—51.0). Of the 263 enrolled patients, 211 had completed their first evaluation for efficacy. The overall ORR, regardless of tumor type, was 15.2% (32/211) with 32 PRs (20 confirmed PRs), and the DCR was 75.4% (159/211) per RECIST 1.1. Twenty-five patients with cervical cancer had an ORR of 28% (7/25). Twenty-six patients with renal cell carcinoma had an ORR of 26.9% (7/26). Twenty-six patients with platinum-resistant ovarian cancer had an ORR of 15.4% (4/26), and 27 patients with NSCLC (with EGFR mutations) had an ORR of 18.5% (5/27). Any-grade TRAEs occurred in 68.8% patients (181/263), with 18.3% Grade ≥3 (48/263). The most common TRAEs were proteinuria (17.5%), hypertriglyceridemia (11.4%), Aspartate aminotransferase (9.9%), Alanine aminotransferase increased (9.5%), Hypoalbuminemia (8.7%), and increased gamma-glutamyl transferase levels (6.8%). Thirty-six patients (13.7%) discontinued PM8002 due to TRAEs. No death-related cases occurred, and most patients remain on treatment. Conclusions: PM8002 showed encouraging antitumor activity and good safety in patients with advanced solid tumors. Phase 1b/IIa of PM8002 as a monotherapy and Phase II combination trials of PM8002 with chemotherapy are ongoing for multiple indications. Clinical trial information: ChiCTR2000040552.

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