A novel liposomal formulation of irinotecan (HE072) has demonstrated promising clinical activity in patients with metastatic triple-negative breast cancer (TNBC), according to results from a recent phase I/II trial conducted between May 2021 and December 2022.
The study enrolled 119 patients, including 101 with metastatic TNBC and 18 with HER2-negative breast cancer brain metastases (BCBM). Participants had received a median of three prior lines of chemotherapy, with 20.8% having previous exposure to PD-1/PD-L1 inhibitors.
Safety Profile and Dosing
At the recommended phase 2 dose (RP2D) of 70 mg/m2, administered every two weeks, the treatment showed a manageable safety profile. The most common treatment-related adverse events included diarrhea (67.3%), leukopenia (59.8%), nausea (57.0%), and anemia (55.1%). Serious treatment-related adverse events occurred in 18.7% of patients, with only 4.2% discontinuing treatment due to adverse events.
Efficacy Outcomes
Among the 87 evaluable TNBC patients, the results were particularly encouraging:
- Partial response rate: 25.3% (95% CI: 16.6-35.8)
- Disease control rate: 67.8%
- Median progression-free survival: 4.8 months
- Median overall survival: 14.1 months
- 12-month survival rate: 59.3%
The treatment showed consistent efficacy across various subgroups, including patients with poor performance status and those with multiple metastatic sites.
Pharmacokinetic Insights
The pharmacokinetic analysis revealed that HE072 primarily remained in its encapsulated form in plasma, with low concentrations of free irinotecan detected throughout the treatment cycle. The mean volume of distribution for total irinotecan at 70 mg/m2 was 3.6 L, suggesting optimal drug delivery characteristics.
Biomarker Analysis
The study included exploratory analyses of UGT1A1 genotype and Topoisomerase I (Topo I) expression. Patients with UGT1A1 homozygosity/compound heterozygosity showed higher rates of grade ≥3 neutropenia compared to wild-type patients (75.0% vs. 31.4%, p=0.042). However, Topo I expression status did not significantly impact survival outcomes.
Clinical Implications
These findings suggest that HE072 could represent a valuable new treatment option for heavily pretreated TNBC patients. The combination of meaningful clinical activity and manageable toxicity profile warrants further investigation in larger clinical trials.
