387P - A prospective phase II study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients (pts) with advanced triple-negative breast cancer (TNBC)

Background

PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. Antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs). AK105, an anti-PD-1 antibody, can effectively prevents PD-1 from binding to PD-L1 and PD-L2, and avoid immune evasion of tumor cells. Anlotinib is a novel antiangiogenic, multi-target tyrosine kinase inhibitor. This investigator initiated trial aims to investigate the efficacy and safety of AK105, anlotinib combined with nab-P as a first-line therapy in pts with advanced TNBC.

Methods

In this multicenter, prospective, single arm, phase 2 study, eligible pts were female aged 18-75 years, with ECOG PS 0-1, who had locally advanced or recurrent/metastatic triple-negative breast cancer. Eligible pts were treated with intravenous AK105 (200 mg on d1), oral anlotinib (12 mg once daily on d1-d14) and intravenous nab-P (125 mg/m2 on d1 and d8). The triplet combination regimen repeated every 21 days until disease progression, death or intolerable toxicity. The primary endpoint is ORR, and the secondary endpoints are DCR, PFS, OS and safety.

Results

From July 2022 to March 2024, 33 patients have been enrolled in this study. Median follow-up was 6.54 months (95% CI 2.68-11.43). Of all the patients whose efficacy could be evaluated (26/33), 1 (3.85%) patient achieved CR; 20 (76.92%), 4 (15.38%) and 1 (3.85%) patients got PR, SD and PD, respectively. ORR was 80.77 % (95% CI 60.65-93.45) and DCR was 96.15% (95% CI 80.36-99.90). The overall mPFS was 11.14 months (95% CI 8.34-18.04), the mOS have not reached. The most common AEs were grade 1 or 2. The grade 3 AEs (incidence ≥ 10%) included were neutropenia (33.33%), leukopenia (12.12%) and elevated AST (12.12%). There were two case of grade 4 neutropenia and one case of grade 4 hypertriglyceridemia. One death (from hepatitis) was considered by the investigators to be related to the trial regimen.

Conclusions

The combination of AK105, anlotinib and nab-P showed better treatment response and tolerable toxicity in the treatment of first-line patients with TNBC.

Clinical trial identification

NCT05244993.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Chiatai Tianqing.

Disclosure

All authors have declared no conflicts of interest.