PPAR-α Inhibitor Plus Nivolumab Shows Promise in RCC

Bruno R. Bastos, MD, medical oncologist at Miami Cancer Institute, Baptist Health South Florida, discusses findings from a study which assessed the pharmacodynamic and radiographic changes among patients with renal cell carcinoma (RCC) who were treated with the combination of nivolumab (Opdivo) and TPST-1120.

The phase 1 study sought to better understand signals to aid in the identification of patients who may benefit from this treatment regimen. According to Bastos and findings presented at the 2024 Genitourinary Cancers Symposium (GU 2024), the pharmacodynamic data observed suggests that there is fatty acid oxidation perturbation and immune gene expression changes, and these are potential biomarkers of clinical benefit.

Additionally, PI3K pathway or IDH mutations may indicate a signal that this combination therapy might benefit this patient population. However, larger studies are needed to further evaluate the combination in patients with RCC.

Transcription:

0:09 | Renal cell carcinoma may have alterations in the lipid of fatty acid metabolism. Some cells really derive from fatty acid oxidation for energy, and renal cell carcinoma may be 1 of those tumors. The idea to use an agent that blocks that fatty acid oxidation is very interesting. In this particular trial, we used the drug TPST-1120, which blocks 6 PPAR-alpha [PPAR-α]. [It was looked at] in multiple doses in phase 1. Then when we reached a dose that was considered to be safe, the recommended phase 2 dose of 400 milligrams [orally twice daily], we combined it with nivolumab in a new cohort with the combination of both.

1:00 | [With] this particular combination, we had 2 patients with renal cell carcinoma who had a response. One of them is the 1 that I am showing in a poster [at GU 2024] which had around a 53% reduction in tumor size, just with the first 2 cycles of the combination of TPST-1120 with nivolumab. In the poster, we show not only the images of this response, but also pharmacodynamic changes in many genes. We did use some genes, which are PPAR-α-associated genes, and we were able to analyze that gene before and after treatment.

1:54 | We could see that this patient who had a response had reduction below baseline and the expression of the 5-6 to PPAR-α-associated genes, which kind of corroborates the idea that the way a treatment [is affected]. It has been associated with the target changes in the genes or gene modulation based on the TPST-1120 activity.