Dual PD-1 and VEGF Blockade Yields Responses in 80% of Patients in Phase 2 Advanced Triple-Negative Breast Cancer Trial

Triple-negative breast cancer lacks common therapeutic targets such as hormone receptors and HER2. Once it progresses to an inoperable or metastatic stage, treatment options are limited and responses are often difficult to sustain. A phase 2 study published in *Nature Medicine* showed that ivonescimab, a bispecific antibody targeting both PD-1 and VEGF, achieved an objective response rate of 80% among evaluable patients when combined with chemotherapy as first-line treatment, providing an early clinical signal for this dual-pathway strategy.

The open-label, single-arm trial, named NCT05227664 and sponsored by Akeso, enrolled 36 women who had not previously received systemic treatment for advanced disease. Patients received ivonescimab at 20 mg per kilogram every two weeks in combination with paclitaxel or nab-paclitaxel. Among 35 patients evaluable for efficacy, 28 achieved complete or partial tumor shrinkage, and the disease control rate was 100%.

With follow-up extended to a median of 22.1 months, the median duration of response was 12.2 months, and median progression-free survival reached 15.2 months. This was longer than the estimated progression-free survival of 9.36 months in an earlier analysis at the end of 2024, reflecting an update as the data matured rather than a direct comparison between two different trials. Overall survival data remain immature.

Ivonescimab is designed as a single antibody that simultaneously blocks PD-1 signaling, which suppresses immune responses, and VEGF, which promotes tumor angiogenesis. In the study, the response rate was 83.3% among patients with a PD-L1 combined positive score of at least 10 and 79.3% among those with a score below 10. The similar figures suggest that efficacy may not be limited to patients with high PD-L1 expression, but the subgroups were very small and remain insufficient to establish biomarker conclusions that could be used for patient selection.

Beyond the efficacy signal, the treatment burden cannot be overlooked. Of the 36 patients, 21, or 58.3%, experienced grade 3 or higher treatment-related adverse events. The study reported no treatment discontinuations or deaths due to treatment-related side effects, but without a control group, it remains difficult to determine how much of the toxicity came from the bispecific antibody, chemotherapy, or their combination. Nor is it possible to directly compare the safety of current immunotherapy regimens.

The main limitations of these findings are the small sample size, the fact that all patients received the experimental combination, and the absence of randomized controls. Therefore, the 80% response rate alone cannot demonstrate that the new combination is superior to the current standard, nor can it rule out bias caused by patient selection. The ongoing randomized phase 3 study NCT06767527 will be the key test of whether ivonescimab can prolong survival, broaden the eligible patient population, and maintain acceptable safety.