CLEAR Study Biomarker Analysis: Lenvatinib/Pembrolizumab vs Sunitinib Advanced Kidney Cancer

The phase 3 CLEAR study (NCT02811861) compared 3 treatments for advanced renal cell carcinoma: lenvatinib (Lenvima) plus pembrolizumab (Keytruda), lenvatinib plus everolimus, and sunitinib (Sutent). Lenvatinib plus pembrolizumab demonstrated significantly longer progression-free survival and overall survival.

At the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, investigators presented data from a biomarker analysis of the CLEAR trial. This study investigated potential markers to predict treatment response.

The lenvatinib and pembrolizumab combination remained more effective than sunitinib regardless of the tested markers, including gene expression signatures related to cell growth, blood vessel formation, and immune response. In the lenvatinib and pembrolizumab arm, PD-L1 status wasn't linked to treatment response. However, a signature associated with MYC was linked to poorer response. the inflamed immune state signature was linked to better response, and a signature related to blood vessel formation was also linked to better response. Standard markers like PD-L1 expression and mutation rates in specific genes weren't linked to treatment response in either arm.

Overall, these findings suggest that the lenvatinib and pembrolizumab combination may be broadly effective across different genetic profiles in advanced RCC and these specific markers may not be helpful for selecting patients for this treatment.

Here, Jaime Merchan, MD, professor, co-leader of the Translational and Clinical Oncology Research Program, and director of the Phase 1 Clinical Trials Program at the Sylvester Comprehensive Cancer Center at the University of Miami, discusses findings from this analysis presented at the 2024 ASCO Meeting.

Transcription:

0:05 | This study was a biomarker analysis of the CLEAR trial trying to determine a correlation between a progression-free survival in the pembrolizumab and lenvatinib versus sunitinib group in correlation with different biomarkers including PD-L1 expression, gene expression signatures, and also genomic abnormalities.

0:28 | The results of the study showed that regardless of any biomarkers, the combination of pembrolizumab and lenvatinib was superior or associated with a better median progression-free survival compared to sunitinib in both expression of PD-L1, different dynamic signatures or gene expression analysis, and also a genomic alterations, specifically mutations of the common renal cell carcinoma gene alterations. The study showed no clear correlation of any benefit with any of these biomarkers.