Abstract PS3-08: Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer treated with First Line PM8002/BNT327 in Combination with Nab-Paclitaxel in Phase Ib/II Study

Abstract Background: PD-L1 and VEGF play important roles in immune evasion and tumoral angiogenesis, promoting cancer growth and metastasis. PM8002/BNT327 is an investigational bispecific antibody targeting PD-L1 and VEGF-A, in development for the treatment of solid tumors. We conducted a Phase Ib/II study of PM8002/BNT327 in combination with nab-paclitaxel in pts with locally advanced or metastatic triple-negative breast cancer (LA/mTNBC) in China. We provide updated results including interim overall survival (OS) since initial reports at SABCS 2023 and ESMO 2024. Methods: 42 Pts with previously untreated LA/mTNBC were enrolled till 11 Apr 2023 to assess the safety and efficacy of PM8002/BNT327 in combination with nab-paclitaxel. All patients received PM8002 at 20 mg/kg (Q2W) and nab-paclitaxel at 100 mg/m2 on the 1st, 8th, and 15th day of each 28-day cycle until unacceptable toxicity or disease progression were observed. Efficacy was assessed every 8 weeks. Primary objectives were safety per CTCAE 5.0 and objective response rate (ORR) per RECIST v1.1 by investigator assessment, with progression free survival (PFS) and overall survival (OS) as secondary objectives. Results: As of 13th Sep 2024, with a median follow-up time of 18.1 months (95% CI 16.9, 19.7), median duration of treatment was 10.0 months (range 2.0-22.0) with 9/42 patients still on treatment. The confirmed ORR (cORR) was 73.8% with a disease control rate (DCR) of 95.2%. The median time to response (TTR) was 1.9 months (95% CI 1.8, 2.0), the median duration of response (DOR) was 11.7 months (95% CI 7.2, 17.3). The matured median PFS was 13.5 months (95% CI 9.4, 18.1) for the ITT population. The median OS was not reached, while the matured 12-month OS rate was 80.8% (95% CI 65,3, 89.9), the matured 15-month OS rate was 78.1% (95% CI 62.1, 88.0) and the nearly matured 18-month OS rate was 72.2% (95% CI 55.2, 83.7). 38 pts had available PD-L1 expression results tested with E1L3N assay. cORR was 76.9% in 13 pts with PD-L1 combined positive score (CPS) < 1 and 72.0% in 25 pts with PD-L1 CPS ≥1. All 9 pts with PD-L1 CPS ≥10 achieved PR. All pts experienced treatment-related adverse events (TRAEs), 59.5% were Grade 3 or 4, no Grade 5 TRAEs were observed. The most common (≥30%) TRAEs included neutropenia, leukocytopenia, anemia, proteinuria, alopecia, hypertriglyceridaemia, hypercholesterolaemia, epistaxis and asthenia. 31.0% of pts experienced immune-related adverse events (irAEs), 9.5% were Grade 3, no Grade 4 or 5 irAEs were observed. The most common irAEs included hyperthyroidism, hypothyroidism and rash. The most common AEs typically associated with VEGF inhibition were hypertension (23.8%) and proteinuria (64.3%) which were mostly Grade 1 or 2. Conclusions: In pts with LA/mTNBC, first-line therapy with PM8002/BNT327 combined with nab-paclitaxel showed clinically meaningful survival outcomes and antitumor activity regardless of PD-L1 status, together with a manageable safety profile. No new safety signals were observed beyond those typically described for anti-PD-1/PD-L1 and anti-VEGF therapies and nab-paclitaxel. A randomized controlled Phase III clinical trial (NCT06419621) of first-line treatment of TNBC in China and a global Phase II trial (NCT06449222) are ongoing in TNBC. Acknowledgements: We would like to thank the pts and their families for their contribution to this trial. This trial was sponsored by Biotheus Inc. PM8002/BNT327 is jointly developed by Biotheus and BioNTech Trial Registration: ClinicalTrials.gov: NCT05918133. Ethics Approval: This study was approved by the Ethics Committee for Drug Clinical Trials, Fudan University Shanghai Cancer Center. Citation Format: Jiong Wu, Jian Zhang, Zhongsheng Tong, Qingyuan Zhang, Yongsheng Wang, Qiao Cheng, Xin Chen, Zhihua Li, Yongmei Yin, Yiqun Du, Yanchun Meng. Interim Overall Survival of Patients with Locally Advanced or Metastatic Triple-Negative Breast Cancer treated with First Line PM8002/BNT327 in Combination with Nab-Paclitaxel in Phase Ib/II Study [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr PS3-08.