Multicohort Phase II Trial of sEphB4-HSA+Pembrolizumab in Solid Tumors

Description

PRIMARY OBJECTIVES:

I. To describe the toxicity associated with the Pembrolizumab-sEphB4-HSA combination in patients with solid tumors (all Cohorts).

II. To identify a signal of activity for each of 4 cohorts of patients:

1. To measure the overall survival (OS) in patients with urothelial carcinoma who have previously been treated with one line of platinum-based therapy in advanced/metastatic setting (Cohort A).
2. To measure the overall survival (OS) in patients with urothelial carcinoma who have previously been treated with at least two lines of therapy, of which at least one is platinum-based, in advanced/metastatic setting (Cohort B).
3. To measure the pathologic complete response (pCR) rate in patients with newly diagnosed urothelial carcinoma of the bladder (platinum eligible and ineligible) treated in neoadjuvant setting prior to radical cystectomy (Cohort C).
4. To measure the PSA response rate in patients with newly diagnosed prostate cancer in neoadjuvant setting prior to radical prostatectomy (Cohort D).

SECONDARY OBJECTIVES:

I. To measure the progression-free survival (PFS) in Cohorts A and B

II. To measure the disease-free survival (DFS) in Cohorts C and D

III. To measure the objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 in Cohorts A and B

IV. To measure the pathologic response rate in newly diagnosed prostate cancer patients in neoadjuvant setting prior to radical prostatectomy in Cohort D

TERTIARY OBJECTIVES:

I. To examine programmed cell death 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), programmed cell death 1 ligand 2 (PD-L2) and EPH receptor B4 (EphB4) expression by tumor cells (TC) as well as immune cells (IC)- macrophages and T cells- in tumor tissue and correlate them with ORR, PFS and OS.

II. To examine the tumor tissue T cell frequency (counts), tumor tissue T cell clonality using T cell receptor (TCR) sequencing, and peripheral blood T cell clonality, pre-treatment and post-treatment and correlate these with ORR, PFS and OS.

III. To measure the phenotype of lymphocytes and myeloid derived suppressor cells (MDSC), in pre and post-treatment blood samples and correlate these with ORR, PFS and OS; an extra blood sample for future studies will also be collected and banked.

IV. To examine peripheral blood circulating tumor cells (CTCs) for enumeration and molecular analysis in pre and post-treatment blood samples, and correlate these with ORR, PFS and OS.

V. To collect and bank tumor tissue. VI. To examine the role of adding positron emission tomography (PET) to a contrast computed tomography (CT) for evaluation of response to treatment.

OUTLINE:

Patients receive recombinant EphB4-HSA fusion protein intravenously (IV) over 60 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 6-12 weeks.