Abstract PO3-06-11: Undated analyses from a Phase Ib open-label study of Pucotenlimab (HX008) in combination with gemcitabine and cisplatin as first-line treatment of metastatic triple-negative breast cancer

Abstract Background: Gemcitabine plus cisplatin (GP) therapy war preferred in China as the first-line therapy for metastatic triple-negative breast cancer (mTNBC), with a median progression-free survival (PFS) of 7.73 months, and a median overall survival (OS) of 19.37 months [1]. Pucotenlimab (HX008) is a novel humanized IgG4 anti-PD-1 monoclonal antibody with an engineered Fc domain. Preliminary results from the phase 1b trial [2] have shown that HX008 combined with GP has a manageable safety profile and demonstrates promising antitumor activity in patients (pts) with mTNBC. Here, we present the updated results from the long-term survival analysis. Methods: Eligible subjects were those who were treatment-naïve mTNBC patients and had measurable lesion. Participants received HX008 at a dose of 3 mg/kg every 3 weeks in combination with chemotherapy (gemcitabine + cisplatin) for 6 cycles and maintained with HX008 until disease progression or unacceptable toxicity occurred. The primary endpoints included overall response rate (ORR) and safety, and the secondary endpoints included duration of response (DoR), PFS, and OS. Results: Between July 2019 and March 2020, a total of 31 pts were enrolled in this study. The median age of patients was 50 years (range 29–69). By the cut-off date (April 24th, 2023), the median follow-up period was 20.7 m (IQR: 12.2, 25.6). The confirmed ORR was consistent with the previously reported data and remains at 74.2% (95% CI: 55.4%, 88.1%). The median PFS was 9.0 months (95% CI, 7.3, 9.3). The median DoR was 7.3 months (95% CI, 5.0, 9.8). The OS was immature, with the result of 23.1 months (95% CI, 13.4, NE), while the 12-m, 24-m and 36-m OS rate was 77.4% (95%CI: 64.0%, 93.6%), 42.7% (95%CI: 28.0%, 65.3%), and 24.4% (95%CI: 11.3%, 52.7%), respectively. The most common grade 3 or 4 treatment-related adverse events included neutropenia (71.0%), leukopenia (45.2%), anemia (38.7%), and thrombocytopenia (32.3%). There was no treatment-related death and no new safety signals were identified. Conclusion: The combination therapy of HX008 plus GP demonstrates favorable clinical efficacy with a manageable safety profile in pts with mTNBC. The combination therapy led to a longer PFS and OS than GP therapy reported previously, regardless of PD-L1 status. The safety profile was consistent with the known toxic effects of each agent. In this updated analysis, no new safety signals were identified. Clinical trial information: NCT04750382 References: [1]. Zhang J, et al. Ann Oncol. (2018). PMID: 29905759 [2]. Cao J, et al. Front Oncol. (2022). PMID: 35982961 Citation Format: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao. Undated analyses from a Phase Ib open-label study of Pucotenlimab (HX008) in combination with gemcitabine and cisplatin as first-line treatment of 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 PO3-06-11.