Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: A single-arm, multicenter, phase 2 study.

person Min Yan Department of Breast Disease, Henan Breast Cancer Center/The affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China info_outline Min Yan, Huimin Lv, Limin Niu, Mengwei Zhang, Huiai Zeng, Shengnan Zhao, Jing Wang, Huihui Sun, Shumin Chen

Authors person Min Yan Department of Breast Disease, Henan Breast Cancer Center/The affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China info_outline Min Yan, Huimin Lv, Limin Niu, Mengwei Zhang, Huiai Zeng, Shengnan Zhao, Jing Wang, Huihui Sun, Shumin Chen Organizations Department of Breast Disease, Henan Breast Cancer Center/The affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China, Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China Abstract Disclosures Research Funding Other Foundation Background: Treatment options for patients with HER2-positive breast cancer after progression on two or more lines of HER2-directed therapies are scarce. Inetetamab, a novel anti-HER2 antibody, exhibits the same binding affinity to HER2 antigen and antibody-dependent cell-mediated cytotoxicity as trastuzumab. Previous studies have demonstrated the treatment potential of PD-1 inhibitor combined with HER2-targeted therapy in HER2-positive gastric or gastroesophageal junction cancer. Utidelone, a genetically engineered epothilone analogue, has shown promising efficacy in heavily pretreated metastatic breast cancer. This study aimed to investigated inetetamab plus camrelizumab (anti-PD-1 antibody) and utidelone in patients with HER2-positive recurrent or metastatic breast cancer who had progressed after at least two lines of HER2-directed therapies with trastuzumab and tyrosine kinase inhibitors (TKIs). Methods: In this phase 2 study (NCT04681287), patients received intravenous camrelizumab (200 mg once every 3 weeks), inetetamab (8 mg/kg loading dose then 6 mg/kg, day 1), and utidelone (30 mg/m 2 , days 1-5) until disease progression or intolerable toxicity. The primary endpoint was 3-month progression-free survival (PFS) rate according to the Response Evaluation Criteria In Solid Tumors, version 1.1. Secondary endpoints included objective response rate (ORR), PFS, overall survival, and safety. Simon’s two-stage design was adopted for this study. Results: Between April 2021 and January 2022, a total of 27 patients were enrolled. As of January 2022, 20 patients could be analyzed. The median number of previous systemic therapies for advanced disease was three. Previous HER2-targeted therapies included trastuzumab (20 [100%]), pyrotinib (17 [85%]), lapatinib (7 [35%]), pertuzumab (3 [15%]), and margetuximab (2 [10%]). The first stage required 10 patients, and 8 of them were free from progression at 3 months. The study proceeded to the second stage for another 31 patients, and the accrual is ongoing. The 3-month PFS rate in 20 patients was 75%. The ORR was 30% (6/20); one (5%) patient achieved complete response. The most common treatment-related adverse events (TRAEs) were peripheral neuropathy (19 [98%]), capillary proliferation (19 [98%]), alopecia (18 [90%]), and fatigue (7 [35%]). Grade ≥3 TRAEs included peripheral neuropathy (2 [10%]) and rash (1 [5%]). No treatment-related treatment discontinuation or deaths occurred. Conclusions: Inetetamab plus camrelizumab and utidelone showed promising efficacy and acceptable safety profile in patients with HER2-positive advanced breast cancer after progression on at least two lines of HER2-directed therapies with trastuzumab and TKIs. Clinical trial information: NCT04681287.