Next Steps in Study of PPAR-α Inhibitor Plus Nivolumab in RCC

Bruno R. Bastos, MD, medical oncologist at Miami Cancer Institute, Baptist Health South Florida, discusses the next steps of a phase 1 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 investigated signals to identify patients who may benefit from this treatment regimen. According to Bastos and findings presented at the 2024 Genitourinary Cancers Symposium (GU 2024), the data suggests that there is fatty acid oxidation perturbation and immune gene expression changes, and these are potential biomarkers of clinical benefit.

“Based on these findings, in seeing the gene expression and lipid changes that have been associated with the mechanism of action of TPST-1120, we notice in this patient that the clinical response and modulation of those genes that have been appropriate with the treatment. The use of targeted agents to this [peroxisome proliferator-activated receptor alpha [PPAR-α], which mainly is involved in fatty acid oxidation in renal cell carcinoma, may be a relevant therapeutic interest,” Bastos says.

Transcription:

0:05 | Based on these findings, in seeing the gene expression and lipid changes that have been associated with the mechanism of action of TPST-1120, we notice in this patient that the clinical response and modulation of those genes that have been appropriate with the treatment. The use of targeted agents to this PPAR-α, which mainly is involved in fatty acid oxidation in renal cell carcinoma, may be a relevant therapeutic interest.

0:40 | Future phase 2 clinical trials of this combination renal cell carcinoma or other agents that block the PPAR-α or studies are needed to know whether or not this experience we see in this particular clinical trial could be seen on a large scale.