A Phase II Clinical Trial of Pembrolizumab Efficacy and Safety in Advanced Renal Medullary Carcinoma

Authors

Chijioke Nze
Pavlos Msaouel
Mohamed H Derbala
Bettzy Stephen
Abdulrahman Abonofal
Funda Meric-Bernstam
Nizar M Tannir
Aung Naing

Publication Date

7-27-2023

Journal

Cancers

Abstract

Background: Renal medullary carcinoma (RMC) is one of most aggressive renal cell carcinomas and novel therapeutic strategies are therefore needed. Recent comprehensive molecular and immune profiling of RMC tissues revealed a highly inflamed phenotype, suggesting the potential therapeutic role for immune checkpoint therapies. We present the first prospective evaluation of an immune checkpoint inhibitor in a cohort of patients with RMC.

Methods: A cohort of patients with locally advanced or metastatic RMC was treated with pembrolizumab 200 mg intravenously every 21 days in a phase II basket trial (ClinicalTrials.gov: NCT02721732). Responses were assessed by irRECIST. Tumor tissues were evaluated for PD-L1 expression and for tumor-infiltrating lymphocyte (TIL) levels. Somatic mutations were assessed by targeted next-generation sequencing.

Results: A total of five patients were treated. All patients had advanced disease, with the majority of patients (60%) having metastatic disease at diagnosis. All patients had rapid disease progression despite pembrolizumab treatment, with a median time to progression of 8.7 weeks. One patient (patient 5) experienced sudden clinical progression immediately after treatment initiation and was thus taken off trial less than one week after receiving pembrolizumab.

Conclusions: This prospective evaluation showed no evidence of clinical activity for pembrolizumab in patients with RMC, irrespective of PD-L1 or TIL levels.

Keywords

immunotherapy, pembrolizumab, renal medullary carcinoma, SMARCB1

DOI

10.3390/cancers15153806

PMID

37568622

PMCID

PMC10417298

PubMedCentral® Posted Date

7-27-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes