The following is a summary of “EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma,” published in the January 2023 issue of Oncology by Sadeghi, et al.

After typical first-line chemotherapy fails, patients with metastatic urothelial carcinoma have a poor prognosis. Due to their low response rates, there was a significant unmet need for immune checkpoint programmed death 1-programmed death ligand 1 antibody.

Patients in the phase II trial got soluble EphB4-human serum albumin (sEphB4-HSA) and pembrolizumab for metastatic urothelial carcinoma that returned or progressed after platinum-based treatment. Tolerance and overall survival (OS) served as the main criteria. The secondary endpoints were toxicity, duration of response, objective response rate (ORR), and progression-free survival (PFS). Results were associated with the expression of the EphrinB2 sEphB4-HSA target.

There were enrolled 70 patients. The average follow-up time was 22.9 months (range, 1.3-54.7). The dosage’s toxicity was tolerable. In the intent-to-treat analysis, the median OS was 14.6 months (95% CI, 9.2 to 21.5) (N = 70). An objective response was seen in 26 patients (37%) (95% CI, 26–48). 4.1 (95% CI, 1.5 to 5.7) months were the median PFS. 46 patients (66%) with EphrinB2 expression had a median OS of 21.5 months (95% CI, 12.4 to not attained), ORR of 52% (95% CI, 37 to 67), and a complete response rate of 24% (11 of 46; 95% CI, 12 to 36) among them. The average PFS was 5.7 (95% CI, 2.7 to 27.9) months. In 88%, 74%, and 69% of the patients, respectively, the response was still there at 6, 12, and 24 months.

Compared to historical data for programmed death 1/programmed death ligand 1 monotherapy, the combination of sEphB4-HSA and pembrolizumab was synergistic with better OS and ORR.

Reference: ascopubs.org/doi/full/10.1200/JCO.21.02923