Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive metastatic breast cancer: Final results from the phase 2 ICU trial.
Authors: Lv Huimin , Yan Min , Sun Tao , Ling Xiaoling , Liu Xinlan , Yang Jin , Zhang Mengwei , Niu Limin , Chen Shumin , Sun Huihui , Wang Jing , Zeng Huiai , Zhao Shengnan , Feng Yajing 
Published: June 2023

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Background: We previously reported (Yan, ASCO 2022) promising efficacy and acceptable safety of anti-HER2 antibody inetetamab in combination with camrelizumab and utidelone regimen in preliminary 20 HER2-positive metastatic breast cancer (MBC) patients who progressed after at least two lines of HER2-directed therapies with trastuzumab and TKIs. Inetetamab is a novel anti-HER2 antibody. Camrelizumab is an anti-programmed death receptor 1 [PD-1] antibody. Utidelone, a genetically engineered epothilone analogue, has shown promising efficacy in heavily pretreated MBC. Here we report the final ICU study results. Methods: In the ICU study (NCT04681287), patients received intravenous camrelizumab (200 mg once every 3 weeks), inetetamab (initial dose of 8 mg/kg, then 6 mg/kg, once every 3 weeks), and utidelone (30 mg/m2, days 1-5, every 3 weeks) 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 and safety. Simon’s two-stage design was adopted for this study. All AEs were graded according to the grading criteria in the Common Terminology Criteria for the Evaluation of Adverse Events, 5th edition. Results: From Apr 23 2021 to Sept 1 2022, a total of 46 HER2-positive MBC patients were enrolled with median age of 52 (range 43-57). As of Jan 18, 2023, the median follow-up was 11.37 months. There were 12 patients (26.09%) with ER+/PR+, 7 patients (15.22%) with ER+/PR-, one patient (2.17%) with ER-/PR+, 26 patients (56.52%) with ER-/PR-. The median number of previous systemic therapies for advanced disease was three. Previous HER2-targeted therapies included trastuzumab (46 [100%]), TKIs (46 [100%], of which pyrotinib 39 [84.78%] and lapatinib 12 [26.09%]), pertuzumab (13 [28.26%]), and margetuximab (3 [6.52%]), T-DM1 or other HER2-ADC (7 [15.22%]). The 3-month PFS rate in 46 patients was 71.84%. The confirmed ORR was 28% (13/46), include one (2.17%) patient achieved complete response. The median PFS was 5.59 months. The most common treatment-related adverse events (TRAEs) were peripheral neuropathy (40 [86.96%]), capillary proliferation (27 [58.7%]), and alopecia (17 [36.96%]). Grade ≥3 TRAEs included rash (3 [6.52%]), peripheral neuropathy (1 [2.17%]) and AST increase (1 [2.17%]). Moreover, there were no grade 4 or above TRAEs. No related treatment discontinuation or deaths occurred. Conclusions: Final efficacy and safety results were consistent with previous ICU study preliminary analyses. The ICU study showed a favorable benefit-risk profile and is an important option for Chinese patients with HER2-positive MBC after at least two lines of HER2-directed therapies with trastuzumab and TKIs. Clinical trial information: NCT04681287 .