EphrinB2 Inhibition, Pembrolizumab Combo Active in R/R Metastatic Urothelial Carcinoma

By Leah Lawrence - Last Updated: August 26, 2022

The combination of soluble EphB4-human serum albumin (sEphB4-HSA) and pembrolizumab appeared to improve overall survival and response rates in patients with recurrent or relapsed metastatic urothelial carcinoma.

“sEphB4-HSA binds EphrinB2 and blocks bidirectional signaling, inhibits tumor growth, and promotes immune cell trafficking into the tumor. Activated T cells also display elevated levels of PD-1 and PD-L1, leading to T-cell exhaustion,” study researchers wrote in The Journal of Clinical Oncology. “In preclinical models, the combination of sEphB4 with PD-1 was found to be more effective than each agent alone supporting a combination trial.”

The phase-2 study enrolled 70 patients with metastatic disease that had recurred or progressed after platinum-based chemotherapy. All patients received sEphB4-HAS plus pembrolizumab.

With a median follow-up of 22.9 months, the median overall survival was 14.6 months in the intent-to-treat group. The researchers noted that this “is substantially longer than the historical data with pembrolizumab monotherapy which had a median OS of 10.1 months.” Median progression-free survival was 4.1 months.

More than one-third (37%) of patients had an objective response.

About two-thirds (66%) of patients expressed EphrinB2. Of these patients, the median overall survival was 21.5 months. More than half (52%) of patients had tumor response, and 24% had a complete response. Progression-free survival in biomarker-positive patients was 5.7 months.

Most patients that responded to treatment on the study continue to maintain their response, the researchers noted.

The most common toxicities included hypertension, fatigue, anemia, anorexia, headache, nausea, proteinuria, rash, hyperuricemia, increase in AST, and pruritis. Treatment was discontinued due to toxicity in 8.6% of patients.

“A phase II study of this combination in metastatic urothelial carcinoma is under way which includes a frontline cohort and an EphrinB2-positive biomarker-selected previously treated cohort,” the researchers wrote.


EphrinB2 Inhibition and Pembrolizumab in Metastatic Urothelial Carcinoma

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