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Metastatic Pancreatic AdenocarcinomaPhase 2NCT02907099

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

A Phase 2 study testing CXCR4 Antagonist BL-8040, Pembrolizumab and Pharmacological Study in people with Metastatic Pancreatic Adenocarcinoma and Recurrent Pancreatic Adenocarcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CXCR4 Antagonist BL-8040, Pembrolizumab and Pharmacological Study
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
1 Dec 2016to 6 Oct 2023
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: A Phase IIb Pilot Study to Assess the Efficacy, Safety, and Pharmacodynamics Effects of Pembrolizumab and BL-8040 in 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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. 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:

  1. 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.

Being tested
CXCR4 Antagonist BL-8040, Pembrolizumab, Pharmacological Study

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CXCR4 Antagonist BL-8040Drug

    Also called BKT140, BL-8040

    Given SC

  • PembrolizumabBiological

    Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475

    Given IV

  • Pharmacological StudyOther

    Correlative studies

Study groups in NCT02907099
Study groupRoleWhat they receive
Treatment (CXCR4 antagonist BL-8040, pembrolizumab)ExperimentalPatients 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.
Receives: Drug: CXCR4 Antagonist BL-8040; Biological: Pembrolizumab; Other: Pharmacological Study

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3 years

Secondary outcomes (3)

  1. 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.

    Measured: pre treatment at baseline and post treatment (2 months)

  2. 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.

    Measured: pre treatment and post treatment, up to 3 years

  3. 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.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Sep 2016 (estimated)
  2. Study start1 Dec 2016
  3. Primary completion6 Oct 2023
  4. Study completion6 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02907099
Sponsor's protocol ID
2016-0410
Other IDs
NCI-2016-01956, 2016-0410
Status last verified
Nov 2024
First submitted
13 Sep 2016
Last updated
19 Feb 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

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