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

NCT02907099 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2016-0410NCI-2016-01956
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

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

Outcome Measures

Primary Outcomes (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

  3 years

Secondary Outcomes (3)

• Quantity of T-Cell Infiltration Pre-treatment and Post Treatment Following Administration of BL-8040 by Itself and BL-8040 With Pembrolizumab

  pre treatment at baseline and post treatment (2 months)

• Quantity of Circulating T-Cells Pre-treatment and Post Treatment Following Administration of BL-8040

  pre treatment and post treatment, up to 3 years

• Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0

  2 years

Study Arms (1)

Treatment (CXCR4 antagonist BL-8040, pembrolizumab)

EXPERIMENTAL

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.

Drug: CXCR4 Antagonist BL-8040; Biological: Pembrolizumab; Other: Pharmacological Study

Interventions

CXCR4 Antagonist BL-8040 DRUG

Given SC

Also known as: BKT140, BL-8040

Treatment (CXCR4 antagonist BL-8040, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (CXCR4 antagonist BL-8040, pembrolizumab)

Pharmacological Study OTHER

Correlative studies

Treatment (CXCR4 antagonist BL-8040, pembrolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Interventions

4-fluorobenzoyl-TN-14003; BKT140; pembrolizumab

Results Point of Contact

• Title: Brandon Smaglo, MD
• Organization: The University of Texas MD Anderson Cancer Center

bgsmaglo@mdanderson.org

(713) 745-8763

Study Officials

• Brandon G. Smaglo, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2016
• First Posted: September 20, 2016
• Study Start: December 1, 2016
• Primary Completion: October 6, 2023
• Study Completion: October 6, 2023
• Last Updated: February 19, 2025
• Results First Posted: February 19, 2025

Record last verified: 2024-11

Locations

US (1)