436P - Preliminary results from a prospective study of inetetamab in combination with pyrotinib and utidelone for HER2-positive metastatic breast cancer (IPUtrial)

Background

Anti-HER2 therapy combined with chemotherapy is the standard therapy for HER2-positive metastatic breast cancer (MBC). Efficacy and safety of inetetamab and pyrotinib in advanced first-line and second-line treatment of HER2-positive breast cancer have been confirmed. Utidelone, a genetically engineered epothilone analogue, has demonstrated antitumor activity in MBC. This study aimed to explore efficacy and safety of the new regimen combined with these three drugs.

Methods

IPUtrial is a prospective, multicenter, single arm, phase 2 study. The study enrolled HER2-positive MBC patients (pts) with first/second line therapy. Pts received inetetamab (8 mg/kg in cycle 1 and 6 mg/kg in subsequent cycles, day 1, IV), pyrotinib (400 mg/d, qd, po) and utidelone (30mg/m², days 1-5, IV) of each 21-day cycle until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) per investigator (INV). The secondary endpoints included INV-assessed progression-free survival (PFS), overall survival (OS) and safety.

Results

At date cutoff (1 Apr 2023), we enrolled 47 pts (29 patients were evaluable for response with median cycles of 8 (4-20) and still undergoing treatment, 19 (65.5%) for the first-line therapy and 10 (34.5%) for the second-line therapy). We reported the efficacy and safety from 29 pts. Partial response (PR) was achieved in 23 pts and stable disease (SD) in 4 pts, the ORR was 79.3% and DCR was 93.1%. The median PFS was not reached. Most of the treatment-related adverse events (TRAEs) were grade 1 or 2 and were considered manageable and reversible. The most common TRAEs was diarrhea (29[100%]). Grade 3 diarrhea was reported in 24 pts (82.8%) with the combination therapy. No treatment-related discontinuation or deaths occurred.

Conclusions

Inetetamab plus pyrotinib and utidelone may be an excellent scheme for HER2-positive metastatic breast cancer. This trial is still ongoing and needs long-term follow-up.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

China Anti-Cancer Association - HER2 Targets China Research Foundation.

Disclosure

All authors have declared no conflicts of interest.