Pembrolizumab and BL-8040 in Metastatic Pancreatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02907099
Recruitment Status : Recruiting
First Posted : September 20, 2016
Last Update Posted : September 14, 2018
Merck Sharp & Dohme Corp.
BioLineRx, Ltd.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:

The goal of this clinical research study is to learn about the effectiveness, safety, and tolerability of pembrolizumab in combination with BL-8040 when given to patients with advanced pancreatic cancer.

This is an investigational study. Pembrolizumab is FDA approved and commercially available for the treatment of melanoma and lung cancer; however, it is not FDA approved for pancreatic cancer. BL-8040 is not FDA approved or commercially available for the treatment of pancreatic cancer.

The study doctor can explain how the study drugs are designed to work.

Up to 15 participants will take part in this study. All will be enrolled at MD Anderson.

Condition or disease Intervention/treatment Phase
Malignant Neoplasms of Digestive Organs Metastatic Pancreatic Cancer Drug: BL-8040 Drug: Pembrolizumab Behavioral: Phone Call Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 2016
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BL-8040 + Pembrolizumab

Patients will initially receive BL-8040 as a single agent, followed by the addition of Pembrolizumab.

Treatment based on three week cycles. In cycle 1, daily dose of BL-8040 administered subcutaneously on Days 1-5 and 8-12. No pembrolizumab administered during cycle 1.

Cycles 2 and beyond Pembrolizumab administered by vein on Day 1 of each 21 day cycle, and BL-8040, administered on Days 1, 4, 8, and 11 of each 21 day cycle.

Study staff calls to check participant's status 30 days after last dose of study drugs, and thereafter, every 12 weeks.

Drug: BL-8040

In cycle 1, a daily dose of BL-8040 1.25 mg/kg administered subcutaneously on Days 1-5 and 8-12.

Cycles 2 and beyond, BL-8040 administered on Days 1, 4, 8, and 11 of each 21 day cycle.

Drug: Pembrolizumab
Cycles 2 and beyond, Pembrolizumab 200 mg administered by vein Day 1 of each 21 day cycle.
Other Names:
  • Keytruda
  • MK-3475
  • SCH-900475

Behavioral: Phone Call
Study staff calls to check participant's status 30 days after last dose of study drugs, and thereafter, every 12 weeks.

Primary Outcome Measures :
  1. Overall Response Rate (ORR) After Treatment with BL-8040 and Pembrolizumab [ Time Frame: 9 weeks ]
    ORR determined by RECIST 1.1 by MD Anderson radiology.

Secondary Outcome Measures :
  1. Duration of Response (DOR) [ Time Frame: Every 10 weeks after last dose of study drugs until disease progression for one year ]
    DOR determined by RECIST 1.1 by MD Anderson radiology.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Have histologically or cytologically confirmed diagnosis of pancreatic adenocarcinoma based on pathology report
  2. Be willing and able to provide written informed consent for the trial.
  3. Be =/> 18 years of age on day of signing informed consent.
  4. 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.
  5. Have documented objective radiographic progression after stopping treatment with first-line therapy and have not yet begun second line therapy. Note: the same image acquisition and processing parameters should be used throughout the study for a given subject.
  6. 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.
  7. Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale.
  8. Have a predicted life expectancy of greater than 3 months.
  9. Demonstrate adequate organ function defined as follows: (All screening labs should be performed within 10 days of treatment initiation); a) Hematological - Absolute neutrophil count (ANC) =/>1,000/mcL, Platelets =/>100,000 / mcL, Hemoglobin =/>9 g/dL or =/>5.6 mmol/L without transfusion or EPO dependency (within 14 days of assessment); b) Renal - Serum creatinine OR Measured or calculated creatinine clearance (should be calculated per institutional standard) (GFR can also be used in place of creatinine or CrCl) =/<1.5 X upper limit of normal (ULN) OR =/>60 mL/min for subject with creatinine levels =/< 1.5 X institutional ULN; c) Hepatic - Serum total bilirubin =/< ULN OR Direct bilirubin =/< ULN for subjects with total bilirubin levels > ULN, AST (SGOT) and ALT (SGPT) =/< 1.5 X ULN, Albumin =/>3.3 mg/dL in the absence of dehydration
  10. (Continuation of criteria # 9) d) Coagulation International Normalized Ratio (INR) or Prothrombin Time (PT) =/<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, 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.
  11. 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.
  12. 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.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Had a solid organ or hematologic transplant.
  5. 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.
  6. 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.
  7. Has radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by PI and radiology review.
  8. Subjects excluded if there is a history of (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease, or active, non-infectious pneumonitis.
  9. Has an active infection requiring systemic therapy.
  10. 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.
  11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  12. 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.
  13. 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.
  14. Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
  15. Has known Hepatitis B or Hepatitis C
  16. 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.
  17. Has a known history of active TB (Bacillus Tuberculosis)
  18. Unable to tolerate a contrast enhanced CT or MRI for staging/restaging purposes
  19. Hypersensitivity to pembrolizumab or any of its excipients.
  20. 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.
  21. 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.
  22. Patients requiring beta blockade are disqualified from participating in this study.
  23. 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.
  24. The use of natural or synthetic cannabinoids.
  25. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02907099

Contact: David Fogelman, MD 713-745-8516

United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Merck Sharp & Dohme Corp.
BioLineRx, Ltd.
Principal Investigator: David Fogelman, MD M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT02907099     History of Changes
Other Study ID Numbers: 2016-0410
NCI-2016-01956 ( Registry Identifier: NCI CTRP )
First Posted: September 20, 2016    Key Record Dates
Last Update Posted: September 14, 2018
Last Verified: September 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by M.D. Anderson Cancer Center:
Malignant neoplasms of digestive organs
Metastatic Pancreatic Cancer
Pancreatic adenocarcinoma
Phone call

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Antineoplastic Agents