Abstract PS08-06: A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002 (Anti-PD-L1 x VEGF-A Bispecific Antibody) in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast Cancer

Abstract Background: PD-L1 and VEGF play important roles in immune evasion and pro-tumor angiogenesis promoting cancer growth and metastasis. PM8002 is a bispecific antibody targeting PD-L1 and VEGF-A for treating cancer. Here, we present results from a Phase Ib/II study of PM8002 in combination with nab-paclitaxel in patients with locally-advanced or metastatic triple-negative breast cancer (TNBC). Methods: 42 patients with locally-advanced or metastatic TNBC (without prior systemic treatment) were enrolled in this Phase Ib/II study to test the safety and efficacy of PM8002 in combination with nab-paclitaxel. The first 6 patients were enrolled during Phase Ib with safety as the primary endpoint, and the remaining patients were enrolled during Phase II with objective response rate (ORR) as the primary endpoint. Each treatment cycle lasts 28 days. All patients received PM8002 at 20 mg/kg (Q2W) and nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th days of each cycle until unacceptable toxicity or disease progression were observed. Tumor responses were evaluated every 8 weeks according to RECIST 1.1. Safety was evaluated according to CTCAE 5.0. Nab-paclitaxel dose was reduced according to toxicity, while PM8002 dose was kept consistent according to body weight. PD-L1 expression in tumors was tested, and subgroup analysis of ORR data stratified by PD-L1 expression was also included. Results: As of June 30, 2023, 42 patients were treated and evaluated at least once for treatment efficacy. The median duration of drug exposure was 4.6 months (min, max: 2.0, 7.6). The best overall ORR was 76.2% (32/42), including 1 complete response (CR) and 31 partial responses (PRs) with 29 objective responses occurring at the patient's first evaluation. The confirmed ORR was 57.2% (24/42) and the overall disease control rate (DCR) was 95.2% (40/42). The median time to response (TTR) was 1.9 months (95% CI:1.8~2.0) and the median best percentage change from baseline for target lesions was -47.2% (Q1, Q3: -56.9%, -33.5%). Among 13 patients with PD-L1 combined positive scores (CPS) 1, the best ORR and DCR were 69.2% (9/13) and 100.0% (13/13), respectively. Among 25 patients with PD-L1 CPS ≥1, the best ORR and DCR were 80.0% (20/25) and 96.0% (24/25), respectively. Among 9 patients with PD-L1 CPS ≥10, the best ORR and DCR were both 100.0% (9/9). At the cut-off date of data analysis, 38 patients were still on treatment with a median progression-free survival (mPFS) of 7.4 months (95% CI: 7.4~NA); 38 patients were censored due to no disease progression or death. The incidence of treatment-related adverse events (TRAEs) was 95.2%, of which 26.2% were Grade 3 or 4; no Grade 5 TRAEs were observed. The incidence of drug-related TRAEs related to PM8002 was 92.9%, of which 23.8% were Grade 3 or 4. The incidence of drug-related TRAEs related to nab-paclitaxel was 95.2%, of which 26.2% were Grade 3 or 4. 1 patient (2.4%) reduced nab-paclitaxel dose due to diarrhea. 1 patient (2.4%) discontinued PM8002 and nab-paclitaxel treatment due to diarrhea. The most common TRAEs related to PM8002 and nab-paclitaxel included neutropenia (69.0%), leukocytopenia (59.5%), anemia (52.4%) and proteinuria (26.2%). The incidence of immune-related adverse events (irAEs) was 11.9%, which included hyperthyroidism, hypothyroidism, and rash. No ≥ Grade 3 irAEs were observed. AEs related to targeting VEGF were also analyzed, including hypertension 19.0% (4.8% at Grade 1, 11.9% at Grade 2, and 2.4% at Grade 3) and proteinuria 26.2% (9.5% at Grade 1, and 16.7% at Grade 2). Conclusions: Rapid, deep, and durable tumor responses were observed for the combination of PM8002 and nab-paclitaxel in patients with first line TNBC. PM8002 did not enhance toxicity that is typically observed for nab-paclitaxel. This Phase II study is still ongoing with plans for entering late-stage clinical development for solid tumors. Citation Format: Jiong Wu, Jian Zhang, Zhongsheng Tong, Qingyuan Zhang, Yong-Sheng Wang, Qiao Cheng, Xin Chen, Zhihua Li, Yongmei Yin. A Phase Ib/II Study to Assess the Safety and Efficacy of PM8002 (Anti-PD-L1 x VEGF-A Bispecific Antibody) in Combination with Nab-Paclitaxel for First Line Treatment of Locally Advanced or Metastatic Triple-Negative Breast Cancer abstract. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS08-06.