Anti-HER2 Antibody Inetetamab Plus Camrelizumab and Utidelone for Pretreated HER2-Positive MBC

The phase 2 ICU study (NCT04681287) previously reported promising efficacy and acceptable safety with combination therapy consisting of the anti-HER2 antibody inetetamab, the anti–PD-1 antibody camrelizumab, and the epothilone analogue utidelone in patients with HER2-positive metastatic breast cancer (MBC).¹

Final study results were reported at the 2023 ASCO annual meeting.² Inclusion criteria included patients with HER2-positive MBC who progressed after ≥2 lines of HER2-directed therapies including trastuzumab and tyrosine kinase inhibitors (TKIs) in the neoadjuvant, adjuvant, and rescue therapy settings. Eligible patients received camrelizumab (200 mg intravenously every 3 weeks), inetetamab (8 mg/kg initially, then 6 mg/kg every 3 weeks), and utidelone (30 mg/m², days 1-5 every 3 weeks) until disease progression or intolerable toxicity. The primary end point was 3-month progression-free survival (PFS) rate; secondary end points included objective response rate (ORR), PFS, and safety.

A total of 46 patients were enrolled in the study; median age was 52 years. Of these, the majority (56.52%) had estrogen receptor (ER)-negative/progesterone receptor (PR)-negative disease, 26.09% had ER-positive/PR-positive disease, 15.22% had ER-positive/PR-negative disease, and 2.17% had ER-negative/PR-positive disease. The study population had received a median of 3 prior systemic therapies for advanced disease. All patients had received trastuzumab and TKIs, including pyrotinib (84.78%) and lapatinib (26.09%); other HER2-targeted therapies were pertuzumab (28.26%), margetuximab (6.52%), and TDM1 or other HER2 antibody–drug conjugate (15.22%).

The median follow-up was 11.37 months. Of the 46 patients evaluable for efficacy, 13 patients achieved a response for a confirmed ORR of 28%, including 1 complete response. The median PFS was 5.59 months, and the 3-month PFS rate was 71.84%.

Treatment-related adverse events (TRAEs; all grades) included peripheral neuropathy (86.96%), capillary proliferation (58.7%), and alopecia (36.96%). Grade ≥3 TRAEs included rash (6.52%), peripheral neuropathy (2.17%), and increased aspartate aminotransferase (2.17%); no grade 4 TRAEs, treatment-related discontinuations, or treatment-related deaths were reported.

Consistent with preliminary analyses of the ICU study, final data also showed promising efficacy and safety, with a favorable benefit-risk profile, with inetetamab plus camrelizumab and utidelone in patients with pretreated HER2-positive MBC who had received ≥2 lines of HER2-directed therapies with trastuzumab and TKIs.

Sources:

1. Yan M, Lv H, Niu L, et al. Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive advanced breast cancer: a single-arm, multicenter, phase 2 study. Abstract presented at: ASCO Annual Meeting, June 3-7, 2022; Chicago, IL. Abstract e13030.
2. Lv H, Yan M, Sun T, et al. Anti-HER2 antibody inetetamab plus camrelizumab and utidelone for pretreated HER2-positive metastatic breast cancer: final results from the phase 2 ICU trial. Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract 1042.