Ivonescimab Displays Preclinical Feasibility in Frontline ccRCC

Ivonescimab (SMT112) has shown mechanistic feasibility in preclinical trials, as well as superior efficacy in lung cancer vs pembrolizumab (Keytruda), suggesting potential for patients with kidney cancer, according to Nazli Dizman, MD.

Dizman, a hematology/oncology fellow at MD Anderson Cancer Center, in a conversation with CancerNetwork®, covered potential data other than findings from the phase 2 IVORY trial (NCT06940518) evaluating ivonescimab in patients with clear cell renal cell carcinoma (ccRCC) that might support the use of the agent in this patient group. She presented data from the trial at the 2025 Kidney Cancer Research Summit.1

Initially, she outlined literature that suggests that ivonescimab has shown mechanistic feasibility and that it has shown that it bolsters outcomes in patients with lung cancer vs pembrolizumab.2 Dizman suggested that the performance in lung cancer could make the agent applicable for kidney cancer, before highlighting the favorable toxicity profile of the agent, including potentially lower rates of discontinuation vs other standards of care.

Dizman concluded by expressing that contemporaries in the kidney cancer field have been “spoiled” by the robust development of new therapies for kidney cancer, while stating that ivonescimab could be a contributor to this trend.

Transcript

The most exciting literature data that we know is that [ivonescimab] mechanistically makes sense. Most of the data in a clinical setting comes from lung cancer. This agent has shown impressive superior outcomes with ivonescimab in lung cancer over pembrolizumab, so there is a possibility that we could utilize that performance in kidney cancer. Toxicity-wise, also, it seems to have a favorable profile, similar to what we would expect from the combination of these 2 mechanistic strategies administered in 2 different ways, but potentially lower rates of treatment discontinuation due to adverse [effects].

My generation in kidney cancer has been spoiled with the development of new therapies in this disease in the past 10 years. Ivonescimab could potentially serve to this momentum that we keep seeing new therapies coming in for kidney cancer. That excites me, and I’m hoping that it would excite other people too.

References

1. Dizman N. Phase II trial of ivonescimab in patients with advanced clear cell renal cell carcinoma previously treated with immune checkpoint blockade: IVORY trial (NCT06940518). Presented at: 2025 Kidney Cancer Research Summit; July 17-18, 2025. Boston, Massachusetts.
2. Xiong A, Wang L, Chen J, et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet. 2025;405(10481):839-849. doi:10.1016/S0140-6736(24)02722-3