Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146.

Authors

• Vicky Makker
• Matthew H Taylor
• Carol Aghajanian
• Allen L Cohn
• Marcia S Brose
• Christopher Di Simone
• Zhu Alexander Cao
• Leah Suttner
• Andrey Loboda
• Razvan Cristescu
• Petar Jelinic
• Robert Orlowski
• Lea Dutta
• Junji Matsui
• Corina E Dutcus
• Yukinori Minoshima
• Mark J Messing

Publication/Presentation Date

1-19-2024

Abstract

BACKGROUND: Lenvatinib plus pembrolizumab demonstrated clinically meaningful benefit in patients with previously treated advanced endometrial carcinoma in Study 111/KEYNOTE-146 (NCT02501096). In these exploratory analyses from this study, we evaluated the associations between clinical outcomes and gene expression signature scores and descriptively summarized response in biomarker subpopulations defined by tumor mutational burden (TMB) and DNA variants for individual genes of interest.

METHODS: Patients with histologically confirmed metastatic endometrial carcinoma received oral lenvatinib 20 mg once daily plus intravenous pembrolizumab 200 mg every 3 weeks for 35 cycles. Archived formalin-fixed paraffin-embedded tissue was obtained from all patients. T-cell-inflamed gene expression profile (Tcell

RESULTS: 93 and 79 patients were included in the RNA-sequencing-evaluable and WES-evaluable populations, respectively. No statistically significant associations were observed between any of the RNA-sequencing signature scores and objective response rate or progression-free survival. Area under the receiver operating characteristic curve values for response ranged from 0.39 to 0.54; all 95% CIs included 0.50. Responses were seen regardless of TMB (≥175 or < 175 mutations/exome) and mutation status. There were no correlations between Tcell

CONCLUSIONS: This analysis demonstrated efficacy for lenvatinib plus pembrolizumab regardless of biomarker status. Results from this study do not support clinical utility of the evaluated biomarkers. Further investigation of biomarkers for this regimen is warranted.

TRIAL REGISTRATION NUMBER: NCT02501096.

Volume

12

Issue

1

ISSN

2051-1426

Published In/Presented At

Makker, V., Taylor, M. H., Aghajanian, C., Cohn, A. L., Brose, M. S., Simone, C. D., Cao, Z. A., Suttner, L., Loboda, A., Cristescu, R., Jelinic, P., Orlowski, R., Dutta, L., Matsui, J., Dutcus, C. E., Minoshima, Y., & Messing, M. J. (2024). Evaluation of potential biomarkers for lenvatinib plus pembrolizumab among patients with advanced endometrial cancer: results from Study 111/KEYNOTE-146. Journal for immunotherapy of cancer, 12(1), e007929. https://doi.org/10.1136/jitc-2023-007929

Disciplines

Medicine and Health Sciences

PubMedID

38242717

Department(s)

Hematology-Medical Oncology Division

Document Type

Article