First-Line Ivonescimab Plus Chemotherapy Demonstrates Efficacy in Advanced TNBC

The PD-1– and VEGF-targeted bispecific antibody ivonescimab (SMT112) in combination with nab-paclitaxel (Abraxane) or paclitaxel demonstrated efficacy and safety in the first-line treatment of patients with locally advanced unresectable or metastatic triple-negative breast cancer (TNBC), according to findings from an ongoing phase 2 trial (NCT05227664) presented at the 2024 ESMO Congress.

“For this trial, we have seen excellent results in the metastatic TNBC [setting] in terms of overall response rate [ORR], progression-free survival [PFS], and safety,” lead investigator Xiaojia Wang, MD, said in an interview with OncLive^®.

Findings showed patients evaluable for efficacy (n = 30) achieved an ORR of 72.4% and a disease control rate of 100%. The median duration of response (DOR) was 7.49 months (95% CI, 3.91–not evaluable [NE]), and the 6-month DOR rate was 68.9% (95% CI, 40.2%-85.9%). The median PFS was 9.30 months (95% CI, 6.24-NE), and the 6-month PFS rate was 73.3% (95% CI, 51.8%-86.3%).

Any-grade treatment-related adverse effects (TRAEs) occurred in all patients, and 53.3% experienced grade 3 or higher TRAEs. Thirty percent of patients had serious TRAEs. However, TRAEs did not lead to treatment discontinuation or death in any patients.

The most common TRAEs reported in at least 20% of patients included decreased white blood cell count (any-grade, 66.70%; grade 3/4, 16.7%), increased alanine aminotransferase levels (56.7%; 6.7%), alopecia (56.7%; 0%), increased aspartate aminotransferase levels (56.7%; 6.7%), decreased neutrophil count (53.3%; 16.7%), anemia (46.7%; 3.3%), rash (33.3%; 3.3%), increased gamma-glutamyltransferase levels (23.3%; 6.7%), hypoesthesia (23.3%; 0%), urinary tract infection (23.3%; 0%), increased blood lactate dehydrogenase levels (20.0%; 0%), hypothyroidism (20.0%; 0%), and decreased weight (20.0%; 0%).

In the interview, Wang highlighted the unmet needs investigators aimed to address in advanced TNBC with this study and expanded on findings from the phase 2 trial.

Wang is an oncologist in the Department of Breast Medical Oncology at the Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, in Hangzhou, China. Additionally, he serves as a key researcher at the Institute of Cancer and Basic Medicine (IBMC) at the Chinese Academy of Sciences.

OncLive: What is the primary mechanism of action of ivonescimab, and what was the rationale for investigating it in patients with metastatic TNBC?

Wang: Ivonescimab is a tetrameric bispecific antibody that targets PD-1 and VEGF.

Metastatic TNBC is [distinct] because the molecular type is heterogeneous, [making] it difficult to treat [with] chemotherapy and other drugs. In clinical practice, patients could progress easily and have shorter survival. In our practice, the guidelines [suggest] chemotherapy like nab-paclitaxel and PD-1 antibodies as the standard regimens.

Anti-VEGF could have use for metastatic TNBC. Therefore, a tetrameric bispecific antibody combining PD-1 and VEGF [antibodies] for [synergistic] antitumor effects. In this trial, we choose ivonescimab plus paclitaxel or nab-paclitaxel for metastatic TNBC in the first line.

What were the key findings from this study?

Thirty patients [enrolled in this trial]. Among 100% of patients, there was no [disease] progression, and the ORR was 72.4%. For patients with a PD-L1 combined positive score of at least 10 [n = 6], the ORR was 83.3%.

Notably, 23.3% of patients had liver metastases at baseline, and 60% of patients had [taxane-based therapy in the neoadjuvant or adjuvant setting]. It can be difficult to treat these patients. Yet, this trial had a high ORR and a [median] PFS of 9.3 months.

What was the safety profile of the regimen?

No patients needed to [permanently discontinue] treatment due to TRAEs. That is [promising] for this regimen.

Reference

Ouyang Q, Wang X, Tian C, et al. The safety and efficacy of ivonescimab in combination with chemotherapy as first-line (1L) treatment for triple-negative breast cancer (TNBC). Ann Oncol. 2024;35:S360-S361. doi:https://doi.org/10.1016/j.annonc.2024.08.295