347MO - The safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC)

Background

Locally advanced unresectable or metastatic TNBC is highly aggressive and has a poor prognosis. Ivonescimab, a tetrameric bispecific antibody targeting PD-1 and VEGF, has the potential to produce complementary and synergistic anti-tumor effects through both pathways via cooperative binding. This study aimed to evaluate the safety and efficacy of ivonescimab in combination with chemotherapy in locally advanced unresectable or metastatic TNBC.

Methods

This was an open-label, multicenter phase II study in patients (pts) with locally advanced unresectable or metastatic TNBC. Pts received ivonescimab at 20 mg/kg Q2W and paclitaxel at 90 mg/m² or nab-paclitaxel at 100 mg/m² on the 1^st, 8^th, and 15^th day of each four-week treatment cycle. The primary endpoints were safety and objective response rate (ORR) by RECIST1.1. The secondary endpoints included duration of response (DoR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results

As of Mar 1, 2024, a total of 30 pts with locally advanced unresectable or metastatic TNBC were enrolled. The median age was 54.0 years (range, 35.4-73.3), 80% of pts had a PD-L1 combined positive score (CPS) <10, and 60% of pts had previously received taxane-based neoadjuvant or adjuvant therapy. The median follow-up was 7.2 months (range: 2.66+, 12.78). A total of 46.7% (14/30) of pts experienced at least one Grade ≥3 treatment-related adverse event (TRAE), but none led to treatment discontinuation or deaths. The most common Grade ≥3 TRAEs with a frequency ≥10% included neutrophil count decreased (16.7%) and white blood cell count decreased (13.3%). Twenty-nine pts had at least one post-baseline tumor assessment; the ORR by investigator assessment was 72.4% (21/29) and the DCR was 100% (29/29). The ORRs of PD-L1 CPS ≥10 and PD-L1 CPS <10 were 83.3% (5/6) and 69.6% (16/23), respectively. The median PFS and OS were not yet mature. The 6-month PFS rate was 68.4% (95% CI: 44.3, 83.8).

Conclusions

Ivonescimab in combination with chemotherapy showed promising anti-tumor activity and tolerable safety as 1L treatment of TNBC. Further trials to confirm the results are warranted.

Clinical trial identification

NCT05227664.

Editorial acknowledgement

Legal entity responsible for the study

Akeso Biopharma, Inc.

Funding

Akeso Biopharma, Inc.

Disclosure

X. Yu: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc. Z.M. Wang: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc. B. Li: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc. Y. Xia: Financial Interests, Personal, Full or part-time Employment: Akeso Biopharma, Inc. All other authors have declared no conflicts of interest.