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Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients receive CXCR4 antagonist BL-8040 SC on days 1-5 and 8-12 of cycle 1 and days 1, 4, 8, and 11 of subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab IV over about 30 minutes on day 1. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

CXCR4 Antagonist BL-8040

Pharmacological Study

Brandon G. Smaglo, MD

This pilot phase IIb trial studies how well pembrolizumab and CXCR4 antagonist BL-8040 work in treating patients with pancreatic cancer that has spread to other places. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. CXCR4 antagonist BL-8040 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pembrolizumab and CXCR4 antagonist BL-8040 may work better in treating patients with pancreatic cancer.

PRIMARY OBJECTIVES:

I. To assess the overall response rate (complete response or partial response) after treatment with CXCR4 antagonist BL-8040 (BL-8040) and pembrolizumab.

SECONDARY OBJECTIVES:

I. To determine the ability of BL-8040 by itself and in combination with pembrolizumab to increase T cell infiltration into the tumor.

II. To determine if BL-8040 treatment results in increases in circulating immune cells.

III. To estimate the safety and tolerability of intravenous administration of pembrolizumab in combination with sub-cutaneously injected BL-8040 in subjects with advanced pancreatic cancer.

EXPLORATORY OBJECTIVES:

I. To evaluate overall response rate (ORR) per immune-related (ir) Response Evaluation Criteria in Solid Tumors (RECIST) and duration of response (DOR), disease control rate (DCR), time to progression (TTP), progression free survival (PFS), and overall survival (OS) per RECIST and irRECIST assessed by MD Anderson investigators.

II. To explore the association between PD-L1 expression by immunohistochemistry, shed PD-L1 level, somatic gene expression profiling and antitumor efficacy of pembrolizumab based on RECIST 1.1 imaging criteria as well as overall survival.

III. To explore the relationship between genomic variation and response to the treatment administered.

IV. Tissue and blood immune monitoring will be conducted through our immune platform group as detailed per the biomarker section based on 3 biopsies done at the following time points: 1) pre-treatment, 2) during the third week of cycle 2 or beginning of cycle 3, and 3) voluntary upon end of cycle 1 (BL-8040 \[BL\] monotherapy) on days 10 to 14.

OUTLINE:

Patients receive CXCR4 antagonist BL-8040 subcutaneously (SC) on days 1-5 and 8-12 of cycle 1 and days 1, 4, 8, and 11 of subsequent cycles. Beginning cycle 2, patients also receive pembrolizumab intravenously (IV) over about 30 minutes on day 1. Cycles repeat every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 10 and 12 weeks.

Pembrolizumab and CXCR4 Antagonist BL-8040 in Treating Patients With Metastatic Pancreatic Cancer

A Phase IIb Pilot Study to Assess the Efficacy, Safety, and Pharmacodynamics Effects of Pembrolizumab and BL-8040 in Patients With Metastatic Pancreatic Cancer

The estimate of the ORR, along with its 95% confidence interval based on the Clopper-Pearson method 32, will be provided. Simon's 2-stage design will be used.

National Cancer Institute (NCI)

M.D. Anderson Cancer Center

Spots Global Cancer Trial Database for recurrent pancreatic adenocarcinoma