Status:
Recruiting
Clinicaltrials.gov identifier:
Sponsor:
University of Southern California
Enrollment:
60
Study Design:
Patients with platinum-refractory metastatic urothelial cancer and no prior PD-(L)-1 therapy were treated with the combination of sEphB4-HSA and pembrolizumab in a single-arm, single-center Phase II study. Treatment was continued until progression or unacceptable toxicity and response was measured every 6 weeks using RECIST 1.1. Tumor tissue for all evaluable patients was tested for B2 expression by immunohistochemistry.
Rationale:
EphrinB2 (B2) is expressed in metastatic urothelial cancer and it blocks immune cell traffic into the tumor. B2 can be blocked by EphrinB4 (B4) which can theoretically increase immune cell traffic and sEphB4-HSA is a fusion protein of soluble EphrinB4 and albumin that binds to EphrinB2. This trial evaluates the combination of pembrolizumab in combination with sEphB4-HSA in previously treated metastatic urothelial cancer with the hypothesis that an influx of immune cells would enhance the response to a anti-PD-(L)-1 therapy.
Endpoints:
The primary endpoint was overall survival (OS) while secondary endpoints were progression free survival (PFS), duration of response (DOR), and objective response rate (ORR).
Comments:
This trial demonstrated impressive results with combination therapy that was more pronounced in those patients with EphrinB2 expression. The combination has received breakthrough designation by the FDA. Given the mechanism of action, it will be interesting to see whether the fusion protein will be synergistic with other immune therapies such as CTLA-4 inhibitors or possibly even BCG.
Results:
69 patients were enrolled. The main sites of disease were the nodes, lungs, and the liver. The median overall survival was 14.4 months. The ORR was 38% with a median PFS of 4.0 and a median DOR of 8 months. Expression of B2 was seen in 46 (65.7%) patients. ORR was 57.5% among B2+ patients with a DOR of 27 months. Among the toxicities, hypertension was the most common attributable to B4. Other toxicities include fatigue, nausea, headache, anorexia, proteinuria, hyperuricemia, rash, anemia, and elevated AST. The percentage of grade 3-4 toxicities seen was 42%.
