Introduction
Triple-negative breast cancer (TNBC) is a particularly aggressive form of breast cancer, accounting for 10–20% of all cases. It is characterized by the absence of estrogen receptor, progesterone receptor, and HER2 expression, which limits the effectiveness of hormonal therapies and HER2-targeted agents. Patients with advanced TNBC have a poor prognosis, and there is a pressing need for more effective first-line treatments. A recent phase 2 trial published in Nature Medicine evaluates the combination of ivonescimab, a PD-1/VEGF bispecific antibody, with chemotherapy in this patient population. The results are encouraging, demonstrating a high objective response rate and a manageable safety profile.
Study Design and Patient Population
This open-label, multicenter, single-arm phase 2 trial enrolled 36 female patients with locally advanced unresectable or metastatic TNBC who had not received prior systemic therapy for their advanced disease. The study was conducted across multiple sites, reflecting a real-world patient population. Eligible patients received ivonescimab at a dose of 20 mg/kg intravenously every two weeks, combined with either paclitaxel (90 mg/m²) or nab-paclitaxel (100 mg/m²) administered on days 1, 8, and 15 of each 4-week cycle. The primary endpoints were safety and investigator-assessed objective response rate (ORR) according to RECIST v1.1 criteria.
Efficacy Results
As of the data cutoff on July 15, 2025, the median follow-up duration was 22.1 months. Among the 35 patients evaluable for efficacy, the objective response rate was an impressive 80.0% (95% confidence interval: 63.1–91.6). This included 2 patients (5.7%) achieving a complete response and 26 patients (74.3%) achieving a partial response. These results suggest that the combination of ivonescimab and chemotherapy has substantial antitumor activity in this difficult-to-treat population. The high response rate is particularly noteworthy given that these patients had not previously received systemic therapy for advanced disease.
Safety Profile
All 36 patients experienced at least one treatment-related adverse event (TRAE), with grade ≥3 TRAEs occurring in 21 patients (58.3%). Importantly, no treatment-related deaths were reported. Immune-related adverse events (irAEs) occurred in 15 patients (41.7%), with grade ≥3 events in 4 patients (11.1%). The safety profile appears consistent with what is known about PD-1 inhibitors and VEGF inhibitors, and the combination was generally manageable. The incidence of high-grade adverse events is comparable to other immunotherapy-chemotherapy combinations in TNBC, and the lack of treatment-related deaths is reassuring.
Implications for Treatment
Triple-negative breast cancer has historically been challenging to treat, especially in the metastatic setting. The introduction of immune checkpoint inhibitors has improved outcomes for some patients, but there remains a need for more effective and durable responses. The bispecific antibody ivonescimab, which simultaneously targets PD-1 and VEGF, offers a novel approach by potentially enhancing antitumor immunity while also inhibiting angiogenesis. The high response rate observed in this trial suggests that this combination could become a promising first-line option for patients with advanced TNBC.
However, it is important to note that this is a phase 2 trial with a relatively small sample size. The results need to be confirmed in larger, randomized phase 3 trials to establish the efficacy and safety relative to standard of care. The trial is registered at ClinicalTrials.gov under identifier NCT05227664, and further investigation is ongoing.
Conclusion
Ivonescimab combined with chemotherapy demonstrates encouraging antitumor activity as first-line therapy for patients with previously untreated advanced triple-negative breast cancer. The 80% objective response rate and manageable safety profile support the further development of this regimen. If confirmed in phase 3 trials, this combination could offer a new standard of care for this patient population, potentially improving outcomes in a disease with historically poor prognosis.
This article is based on reporting by Nature Medicine. Read the original article.
Originally published on nature.com
