The results of a phase 2 interventional clinical study that were previously reported showed promising efficacy and acceptable safety with the combination 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.1
The final study results were reported at the 2023 ASCO annual meeting.2 To be included in the study, patients had to have HER2-positive, metastatic breast cancer that 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 adverse events. The primary end point was the 3-month progression-free survival (PFS) rate; the secondary end points included objective response rate (ORR), PFS, and safety.
A total of 46 patients were enrolled in the study, and the median patient age was 52 years. A majority (56.52%) of the patients 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 previous 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 trastuzumab emtansine or other HER2 antibody–drug conjugates (15.22%).
At the data cutoff, the median follow-up was 11.37 months. In all, 13 of the 46 patients who were evaluable for efficacy 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 2022 study results, the final data also showed promising efficacy and safety, as well as a favorable benefit-risk profile, with inetetamab plus camrelizumab and utidelone in patients with pretreated HER2-positive metastatic breast cancer who received ≥2 lines of HER2-directed therapies with trastuzumab and TKIs.
- 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.
- 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.