Inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: a prospective, single-arm, phase 2 study

Background: The efficacy and safety of anti-HER2 therapy and immune checkpoint inhibitors combined with chemotherapy to treat HER2-positive advanced breast cancer that has failed standard HER2-directed therapies is unknown. This study evaluated the efficacy and safety of a novel, fully China-developed combination therapy—comprising inetetamab (an anti-HER2 monoclonal antibody), camrelizumab (an anti-PD-1 antibody), and utidelone (a microtubule inhibitor)—in this treatment-refractory population. Methods: The ICU study (NCT04681287) was a single-arm, multicentre, phase 2 trial conducted at five centres in China. Patients with HER2-positive MBC who had experienced progression on prior trastuzumab and TKIs were enrolled. The primary endpoint was the 3-month progression-free survival (PFS) rate in the per-protocol population. Results: A total of 48 patients with a median of three previous systemic therapies for advanced disease (range, 1–4) were enrolled (median follow-up duration 43.0 months). The 3-month PFS rate in 46 patients was 71.67% (95% CI: 59.7–85.9). The most common any-grade treatment-emergent adverse events (TEAEs) were peripheral neuropathy (87.2%, two events were grade 3) and reactive cutaneous capillary endothelial proliferation (57.4%, all grade 1–2). There were no grade 4 or 5 TEAEs. Conclusions: The combination of inetetamab, camrelizumab, and utidelone demonstrated promising efficacy and a manageable safety profile in heavily pretreated patients with HER2-positive MBC. These findings support this regimen as a viable treatment option in this setting and warrant further investigation in randomized controlled trials. Trial registration: The study was registered at ClinicalTrials.gov with the identifier NCT04681287.