EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma. Issue 3 (19th August 2022)

• Record Type: Journal Article
• Authors: Sadeghi, Sarmad; Quinn, David; Dorff, Tanya; Pal, Sumanta; Groshen, Susan; Tsao-Wei, Denice; Parikh, Rahul; Devitt, Michael; Parikh, Mamta; Jackovich, Alexandra; Ruel, Nora; Vogelzang, Nicholas; Burgess, Earle; Siddiqi, Imran; Gill, Inderbir S.; Lara, Primo N.; Dreicer, Robert; Gill, Parkash S.
• Is Part Of: Journal of clinical oncology. Volume 41:Issue 3(2023)
• Page Start: 640
• Page End: 650
• Publication Date: 2022-08-19
• Subjects: Oncology -- Periodicals; Cancer -- Periodicals; Oncology; Medical Oncology; Cancérologie -- Périodiques; Cancer -- Périodiques; Cancérologie; Cancer; Oncology; Oncologia; Càncer; Periodicals; 616.994
• DOI: 10.1200/JCO.21.02923
• Languages: English
• ISSNs: 0732-183X

Abstract

Abstract : PURPOSE: Patients with metastatic urothelial carcinoma have poor prognosis after failure of standard first-line chemotherapy. Immune check point programmed death 1-programmed death ligand 1 antibodies have low response rates and thus there exists a major unmet need. MATERIALS AND METHODS: In this phase II trial, patients with metastatic urothelial carcinoma that recurred or progressed after platinum-based chemotherapy received soluble EphB4-human serum albumin (sEphB4-HSA) in combination with pembrolizumab. The primary end points were tolerability and overall survival (OS). The secondary end points were progression-free survival (PFS), objective response rate (ORR), duration of response, and toxicity. The expression of sEphB4-HSA target EphrinB2 was correlated with outcomes. RESULTS: Seventy patients were enrolled. The median follow up was 22.9 months (range, 1.3-54.7). The regimen had acceptable toxicity. In the intent-to-treat analysis (N = 70), the median OS was 14.6 months (95% CI, 9.2 to 21.5). Twenty-six (37%) patients had an objective response (95% CI, 26 to 48). The median PFS was 4.1 (95% CI, 1.5 to 5.7) months. Forty-six (66%) patients expressed EphrinB2, and among them, the median OS was 21.5 months (95% CI, 12.4 to not reached), the ORR was 52% (95% CI, 37 to 67), including a complete response rate of 24% (11 of 46; 95% CI, 12 to 36). The median PFS was 5.7 (95% CI, 2.7 to 27.9) months. Response was maintained at 6, 12, and 24 months in 88%, 74%, and 69% of the patients, respectively. CONCLUSION: The combination of sEphB4-HSA and pembrolizumab appears synergistic with improved OS and ORR compared with historical data for programmed death 1/programmed death ligand 1 monotherapy.