c-MET expression by IHC and response to cabozantinib in patients with relapsed, refractory germ-cell tumor: A single-arm phase II trial.

Abstract

e17015 Background: Cabozantinib, a multi-targeted tyrosine kinase inhibitor targeting c-MET, VEGFR, and AXL, shows clinical benefit in patients (pts) with refractory germ-cell tumor (GCT) 1 . High c-MET expression by immunohistochemistry (IHC) has shown worse prognosis in solid tumors, though MET expression has not shown to correlate with treatment response and outcomes with cabozantinib 2,3 . We evaluate MET expression by IHC as a biomarker of response to cabozantinib in pts with relapsed, refractory GCT. Methods: As part of a previously reported phase II clinical trial of cabozantinib in pts with relapsed, refractory GCT, archival tissue tumor was obtained optionally at enrollment. Formalin-fixed paraffin embedded tumor blocks or freshly cut formalin-fixed paraffin embedded slides were analyzed for IHC analysis of MET protein levels using a lab antibody. MET expression was defined as high or low based on a cutoff of 50% or higher of the tumor tissue staining with an intensity of 2+ or 3+. Progression free survival was estimated using the Kaplan-meier method and compared between groups using the log-rank test. Results: Clinical characteristics of pts included have been described previously 1 . Overall, 44 patients were enrolled and evaluable, and the clinical benefit rate was 43.2%. 21 of 44 (48%) evaluable pts had archival tissue available for analysis. Eight pts (38.1%) had high MET expression; 13 (61.9%) had low expression. Of those with high MET expression, 4 (50%) had progressive disease (PD), while 4 (50%) had stable disease (SD). In those with low MET expression, 4 (30.8%) had PD, 8 (61.5%) had SD, and 1 (7.7%) had a partial response (PR). Clinical benefit rate for high vs low MET expression was 50% vs 69.2%. Median PFS for those with low MET expression was 119.8 days (35.7-204); Median PFS for those with high expression was 59.8 days (14.9-104.6) (p = 0.205). Conclusions: MET expression levels did not correlate with response and outcomes to cabozantinib in pts with relapsed, refractory GCT. 1 King J, et al. A phase II trial of cabozantinib in relapsed, refractory germ-cell tumors. To be presented at GU ASCO 2026. 2 Gibney GT, et al. c-MET is a prognostic marker and potential therapeutic target in clear cell renal cell carcinoma. Ann Oncol 2013; 24: 343-349. 3 Choueiri TK, et al. Cabozantinib versus everolimus in advanced renal cell carcinoma (METEOR): final results from a randomized, open-label, phase 3 trial. Lancet Oncol 2016; 17: 917-27.