Pembrolizumab And CXCR4 Antagonist BL-8040 In Treating Patients With Metastatic Pancreatic Cancer

Study Overview

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

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.

Metastatic Pancreatic Adenocarcinoma
Recurrent Pancreatic Adenocarcinoma
Stage IV Pancreatic Cancer AJCC v6 and v7

DRUG: CXCR4 Antagonist BL-8040
BIOLOGICAL: Pembrolizumab
OTHER: Pharmacological Study

2016-0410
NCI-2016-01956 (REGISTRY Identifier) (REGISTRY: CTRP (Clinical Trial Reporting Program))
2016-0410 (OTHER Identifier) (OTHER: M D Anderson Cancer Center)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2016-09-13	Results First Submitted 2024-08-30	Last Update Submitted that met QC Criteria 2025-01-28
First Submitted that Met QC Criteria 2016-09-15	Results First Submitted that Met QC Criteria 2025-01-28	Last Update Posted (ACTUAL) 2025-02-19
First Posted (ACTUAL) 2016-09-20	Results First Posted 2025-02-19	Last Verified 2024-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: Treatment (CXCR4 antagonist BL-8040, pembrolizumab) 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 y	DRUG: CXCR4 Antagonist BL-8040 Given SC BIOLOGICAL: Pembrolizumab Given IV OTHER: Pharmacological Study Correlative studies

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: Treatment (CXCR4 antagonist BL-8040, pembrolizumab)

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 y

DRUG: CXCR4 Antagonist BL-8040

Given SC

BIOLOGICAL: Pembrolizumab

Given IV

OTHER: Pharmacological Study

Correlative studies

Primary Outcome Measures	Measure Description	Time Frame
Overall Response Rate	To assess the overall response rate (complete response or partial response) PER RECIST 1.0 after treatment with CXCR4 antagonist BL-8040 (BL-8040) and pembrolizumab	3 years

Secondary Outcome Measures	Measure Description	Time Frame
Quantity of T-Cell Infiltration Pre-treatment and Post Treatment Following Administration of BL-8040 by Itself and BL-8040 With Pembrolizumab	Biomarker Analysis (TCR analysis, flow cytometry panel) of biopsy core samples was utilized to detect the presence and amount of T Cell infiltration into the tumor tissue.	pre treatment at baseline and post treatment (2 months)
Quantity of Circulating T-Cells Pre-treatment and Post Treatment Following Administration of BL-8040	Biomarker Analysis (TCR analysis, flow cytometry panel) of biopsy core samples was utilized to detect the Quantity of circulating T-Cells into the tumor tissue.	pre treatment and post treatment, up to 3 years
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0	Utilizing CTCAE v4.0, the number of treatment-related adverse events was recorded.	2 years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report
Be willing and able to provide written informed consent for the trial
Have measurable disease based on RECIST 1.1; target lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
Have documented objective radiographic progression after stopping treatment with first-line therapy; Note: the same image acquisition and processing parameters should be used throughout the study for a given subject
Be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion from a metastatic site; newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on day 1; subjects for whom newly-obtained samples cannot be provided (e.g. inaccessible or subject safety concern) may submit an archived specimen only upon agreement from Merck; the specimen must be from a biopsy site that would be accessible for at least one subsequent biopsy after initiation on the trial
Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
Have a predicted life expectancy of greater than 3 months
Absolute neutrophil count (ANC) >= 1,000 /mcL (performed within 10 days of treatment initiation)
Platelets >=100,000 /mcL (performed within 10 days of treatment initiation)
Hemoglobin >= 9 g/dL or >= 5.6 mmol/L without transfusion or erythropoietin (EPO) dependency (within 14 days of assessment) (performed within 10 days of treatment initiation)
Serum creatinine OR measured or calculated creatinine clearance (should be calculated per institutional standard) (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) =< 1.5 X upper limit of normal (ULN) OR >= 60 mL/min for subject with creatinine levels =< 1.5 X institutional ULN (performed within 10 days of treatment initiation)
Serum total bilirubin =< ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > ULN (performed within 10 days of treatment initiation)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) =< 1.5 X ULN (performed within 10 days of treatment initiation)
Albumin >= 3.3 mg/dL in the absence of dehydration (performed within 10 days of treatment initiation)
International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants (performed within 10 days of treatment initiation)
Have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication (cycle 1, day 1) (female subjects of childbearing potential); if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
Female subjects of childbearing potential must be willing to use an adequate method of contraception; contraception, for the course of the trial through 120 days after the last dose of trial drug; note: abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject; male subjects of childbearing potential must agree to use an adequate method of contraception; contraception, starting with the first dose of trial therapy through 120 days after the last dose of trial therapy

Has pancreatic tumor other than adenocarcinoma, including: acinar cell carcinoma, pancreaticoblastoma, malignant cystic neoplasms, endocrine neoplasms, squamous cell carcinoma; vater and periampullary duodenal or common bile duct malignancies
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy, herbal/complementary oral or IV medicine, or used an investigation device within 4 weeks of the first dose of treatment
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
Had a solid organ or hematologic transplant
Has active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs); replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
Has a diagnosed additional malignancy within 1 year prior to first dose of study treatment with the exception of curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin and/or curatively resected in situ cervical and/or breast cancers
Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by principal investigator (PI) and radiology review
Subjects excluded if there is a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease, or active, non-infectious pneumonitis
Has an active infection requiring systemic therapy
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator, including dialysis
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
Has received prior immunotherapy with agents that target PD-1, PD-L1, PD-L2, CTLA-4, OX-40, or CD-137 agents, or if the subject has previously participated in Merck pembrolizumab clinical trials
Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
Has known hepatitis B or hepatitis C
Has received a live vaccine within 30 days of planned start of study therapy (cycle 1, day 1); Note: the killed virus vaccines used for seasonal influenza vaccines for injection are allowed; however intranasal influenza vaccines (e.g., FluMist) are live attenuated vaccines and are not allowed
Has a known history of active TB (Bacillus tuberculosis)
Unable to tolerate a contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) for staging/restaging purposes
Hypersensitivity to pembrolizumab or any of its excipients
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to such agents administered more than 4 weeks earlier
Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e., =< grade 1 or at baseline) from adverse events due to a previously administered small molecule agent; a. Note: subjects with =< grade 2 neuropathy or alopecia are an exception to this criterion and may qualify for the study; b. Note: if subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy
Patients requiring beta blockade are disqualified from participating in this study
Patients who, in the estimation of the treating physician or primary investigator, have had a clinical deterioration of their ECOG performance within the month prior to enrollment
The use of natural or synthetic cannabinoids
Patients with unstable angina, new onset angina within the last 3 months, myocardial infarction within the last 6 months, and current congestive heart failure New York Heart Association class III or higher

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

PRINCIPAL_INVESTIGATOR: Brandon G. Smaglo, MD, M.D. Anderson Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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