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Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients (COMBAT/KEYNOTE-202) (COMBAT)

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.
 
ClinicalTrials.gov Identifier: NCT02826486
Recruitment Status : Recruiting
First Posted : July 11, 2016
Last Update Posted : January 3, 2020
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
BioLineRx, Ltd.

Brief Summary:
This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL8040/ Pembrolizumab in combination with liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV) in subjects with metastatic pancreatic adenocarcinoma.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: BL-8040 Drug: Pembrolizumab Drug: Chemotherapy of Onivyde Phase 2

Detailed Description:

This will be an open-label, two-cohort, phase IIa study in subjects with metastatic pancreatic adenocarcinoma.

The study will be comprised of 2 cohorts,. Each includes approximately 40 subjects with unresectable metastatic pancreatic adenocarcinoma.

Each cohort study consists of two periods:

  • Monotherapy period: One week, with BL-8040 administered daily on days 1-5.
  • Combination therapy:

Cohort 1: Three-week cycles of a combination of BL-8040 administered three times a week (TIW) and pembrolizumab administered once every three weeks.

Cohort 2: Onivyde®/5-FU/LV every 2 weeks, pembrolizumab once every 3 weeks and BL-8040 twice a week.

Cohort 1: Subjects with metastatic pancreatic adenocarcinoma will be enrolled and receive BL-8040 monotherapy for five days followed by a combination treatment of BL-8040 and pembrolizumab. During the monotherapy period, eligible subjects will receive daily subcutaneous (SC) injections of BL-8040 (1.25 mg/kg) on Days 1 - 5.

From Day 8, subjects will begin a combination period consisting of treatment with SC BL-8040 TIW and pembrolizumab once every three weeks. The combination therapy will continue for up to 35 cycles of pembrolizumab approximately two years), or until progression, clinical deterioration or Early Termination, whichever comes first.

Cohort 2: Subjects with metastatic pancreatic adenocarcinoma that have progressed following first-line treatment with gemcitabine-based chemotherapy will be enrolled and receive BL-8040 monotherapy for five days followed by a combination treatment of BL-8040, pembrolizumab and chemotherapy. During the monotherapy period, eligible subjects will receive daily SC injections of BL-8040 on Days 1 - 5.

From Day 8, subjects will begin a combination period consisting of:

  • IV Onivyde® followed by IV leucovorin (LV), followed by IV fluorouracil (5-FU), every 2 weeks.
  • Pembrolizumab every three weeks.
  • BL-8040 twice a week

The combination therapy will continue for up to 35 treatments (approximately two years), or until progression, clinical deterioration or Early Termination, whichever comes first.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIa, Multicenter, Open-label Study to Assess the Safety and Efficacy of the Combination of BL-8040 and Pembrolizumab in Patients With Metastatic Pancreatic Cancer, the COMBAT Study
Actual Study Start Date : September 2016
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: BL-8040 plus pembrolizumab (Keytruda®)

BL-8040 monotherapy 1.25 mg/kg subcutaneous(SC) injections daily on days 1-5 of week 1 of treatment.

Combination therapy period begins following monotherapy treatment and consists of:

  • Pembrolizumab 200mg once every three weeks.
  • Beginning on Day 10, BL-8040 three times a week
Drug: BL-8040
BL-8040 subcutaneous(SC) injections

Drug: Pembrolizumab
pembrolizumab will be given as a 30-minute IV infusion
Other Name: Keytruda

Experimental: BL-8040 plus pembrolizumab (Keytruda®) plus Onivyde chemo

BL-8040 monotherapy 1.25 mg/kg subcutaneous(SC) injections daily on days 1-5 of week 1 of treatment.

Combination therapy period begins following monotherapy treatment and consists of:

  • IV Onivyde® 70 mg/m2 over 90 minutes followed by IV leucovorin (LV) 400 mg/m2 over 30 minutes or according to local standard, followed by IV fluorouracil (5-FU) 2400 mg/m2 over 46 hours, every 2 weeks.
  • Pembrolizumab 200mg once every three weeks.
  • Beginning on Day 10, BL-8040 twice a week and following the chemotherapy dosing.
Drug: BL-8040
BL-8040 subcutaneous(SC) injections

Drug: Pembrolizumab
pembrolizumab will be given as a 30-minute IV infusion
Other Name: Keytruda

Drug: Chemotherapy of Onivyde
• IV Onivyde® followed by IV leucovorin (LV), followed by IV fluorouracil (5-FU), every 2 weeks.
Other Name: Onivyde / Leucovorin (LV) / 5FU




Primary Outcome Measures :
  1. Objective response rate (ORR) assessed by imaging according to RECIST 1.1 criteria [ Time Frame: Change in response between screening, end of monotherapy (Day 5), end of cycle 2 (Day 28) and approximately every 63 days until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months. ]
    response is determined by assessment of target lesions identified in CT or MRI imaging


Secondary Outcome Measures :
  1. Objective response rate (ORR) assessed by imaging according to irRECIST [ Time Frame: Change in response between screening, end of monotherapy (Day 5), end of cycle 2 (Day 28) and every 63 days until the date of confirmed progression assessed up to 2 years, or date of death from any cause. ]
    repeat imaging will be done for confirmation of initial progressive disease

  2. Overall survival [ Time Frame: Through study completion, an average of 2 years, and follow-up until date of death up to 100 weeks. ]
  3. Progression-free survival (PFS) by imaging (RECIST 1.1) [ Time Frame: through study completion, an average of 2 years ]
    imaging will be assessed according to RECIST 1.1

  4. Disease Control [ Time Frame: through study completion, an average of 2 years ]
    Sum of PRs, CRs and SDs


Other Outcome Measures:
  1. Safety as measured by number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment with BL-8040 alone or in combination with pembrolizumab [ Time Frame: study treatment duration, up to 2 years ]
    safety assessment based on CTCAE version 4.03 criteria for adverse events and clinical laboratory parameters

  2. Tolerability of BL-8040 as monotherapy and in combination with pembrolizumab by review of adverse events and clinical laboratory parameters [ Time Frame: study treatment duration, up to 2 years ]

    Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment)

    Assessment based on CTCAE version 4.03 criteria for adverse events and clinical laboratory parameters.


  3. Incidence of early discontinuation of subjects. [ Time Frame: study treatment duration, up to 2 years ]
    discontinuation of study treatment for any reason

  4. Incidence of early discontinuation due to adverse events. [ Time Frame: study treatment duration, up to 2 years + 90 days for SAE follow-up ]
    adverse events will be recorded based on CTCAE version 4.03 criteria and MedDRA



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  1. 18 years and older.
  2. Patients must sign a written informed consent prior to entering the study.
  3. Histologically confirmed (either previously or newly biopsied) metastatic unresectable pancreatic adenocarcinoma, including with intraductal papillary mucinous neoplasm.
  4. Have measurable disease (≥ 1 measurable lesion) based on Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 as determined by the site study team. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  5. Previous treatment lines

    1. Cohort 1: Have documented objective radiographic progression after stopping treatment with first-line or further therapy, i.e. chemotherapy and or radiotherapy. Surgery not followed with neoadjuvant therapy will not be considered as first-line therapy.
    2. Cohort 2: Have documented objective radiographic progression after stopping treatment with first-line, gemcitabine-based chemotherapy. Only primary metastatic patients will be allowed to participate. Patients with previous surgery for their pancreatic cancer will not be allowed to participate.
  6. Willing to submit an evaluable tumor tissue sample, preferably from a liver metastasis, unless tumor is considered inaccessible or biopsy is otherwise considered not in the subject's best interest
  7. Complete resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the subject received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  8. ECOG status ≤1.
  9. Life expectancy of at least 3 months.
  10. Adequate organ function at Baseline as defined below. All laboratory assessments should be performed within 10 days of treatment initiation

    1. Hematological:

      • White blood cell (WBC) ≥ 2,500/mm^3
      • Absolute neutrophil count

        • Cohort 1: ≥ 1000 /mm^3
        • Cohort 2: ≥ 1500 /mm^3
      • Platelet count ≥ 100,000/mm^3
      • Hemoglobin ≥9 g/dL or ≥5.6 mmol/L
      • Hematocrit ≥30%
    2. Renal function:

      • Creatinine ≤1.5x Upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR]) can also be used in place of creatinine or (CrCl) > 60 mL/min for subject with creatinine levels > 1.5x institutional ULN

    3. Hepatic function:

      • Total Bilirubin: within institutional normal ranges
      • Aspartate Aminotransferase/Serum Glutamic Oxaloacetic Transaminase (AST/SGOT) and Alanine Transaminase/Serum Glutamic Pyruvic Transaminase (ALT/SGPT): ≤2.5xULN OR ≤5xULN for subjects with liver metastases
    4. Coagulation:

      • INR or PT: ≤1.5xULN 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): ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  11. Subjects must use effective contraception:

    1. Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative urine or serum pregnancy test within 72 hours prior to taking study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the subject to be eligible. Non-childbearing potential is defined as (by other than medical reasons):

      • ≥45 years of age and has not had menses for over 2 years
      • Amenorrhoeic for > 2 years without a hysterectomy and oophorectomy and a Follicle Stimulating Hormone (FSH) value in the postmenopausal range upon pretrial (Screening) evaluation
      • Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation at least 6 weeks prior to Screening. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure otherwise the subject must be willing to use two adequate barrier methods throughout the study, starting with the Screening visit through 120 days after the last dose of study therapy. Information must be captured appropriately within the site's source documents
    2. Male subjects must agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria:

  1. Has a 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. For Cohort 2 only: subjects with a bowel obstruction.
  3. Has an active infection requiring systemic therapy or has an uncontrolled infection.
  4. Has a known additional malignancy that is progressing or requires active treatment. Exceptions are adequately treated basal cell or squamous cell carcinoma that has undergone potentially curative therapy or carcinoma in situ of the cervix.
  5. Has an underlying medical condition that would preclude study participation.
  6. Has a disease that is suitable for therapy administered with curative intent.
  7. Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  8. 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.
  9. 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 AE due to agents administered more than 4 weeks earlier.
  10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or has not recovered (i.e., ≤ Grade 1 or at Baseline) from AE due to a previously administered agent .
  11. An active autoimmune disease that has required systemic treatment in the 2 years preceding the study (i.e., with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs). Note: 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 and is allowed.
  12. Has received transfusions of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including Granulocyte Colony Stimulating Factor [G-CSF], GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
  13. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  14. Has a history of interstitial lung disease.
  15. O2 saturation < 92% (on room air).
  16. For both Cohorts: Has 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. For Cohort 2: has ventricular arrhythmias or uncontrolled blood pressure, or severe arterial thromboembolic events less than 6 months prior to study initiation.
  17. 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.
  18. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  19. 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. Women with a positive pregnancy test within 72 hours from Baseline.
  20. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or if the subject has previously participated in Merck MK-3475 clinical trials.
  21. Has a positive HIV test at Screening or at any time prior to Screening. Patients without a prior positive HIV test result will undergo an HIV test at Screening, unless not permitted per local regulations.
  22. Has known active Hepatitis B (defined as having a positive Hepatitis B surface antigen (HBsAg) test at Screening) or Hepatitis C (defined as having a positive HCV antibody test or a positive HCV RNA test at Screening)
  23. Has known history of Chronic Hepatitis B or C
  24. Has received a live vaccine within 30 days of the planned start of study therapy. Seasonal flu vaccines that do not contain live virus are permitted.
  25. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Note: Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging using the identical imaging modality for each assessment, either MRI or computerized tomography (CT) scan, for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to Baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 14 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
  26. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
  27. Cohort 2: Has clinical ascites requiring treatment

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 ClinicalTrials.gov identifier (NCT number): NCT02826486


Contacts
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Contact: Liat Rahamim 972-86429100 ext 147 liatr@biolinerx.com
Contact: Tzipi Lustig, DVM 972-8649100 ext 136 tzipil@biolinerx.com

Locations
Hide Hide 30 study locations
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United States, Arizona
Mayo Clinic Active, not recruiting
Phoenix, Arizona, United States, 85054
Honor Health Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Margaux Steinbach    480-323-1562    Margaux.Steinbach@HonorHealth.com   
Principal Investigator: Erkut Borazanci, MD         
United States, Louisiana
Ochsner Medical Center Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Sharon Jerdonek, RN    504-842-3929    sharon.jerdonek@ochsner.org   
Principal Investigator: Robert Ramirez, MD         
United States, Massachusetts
Massachusetts General Hospital (MGH) Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ashley O'Meara    617-643-5411    alomeara@mgh.harvard.edu   
Principal Investigator: Colin Weekes, MD         
Beth Israel Deaconess Medical Center (BIDMAC) Recruiting
Boston, Massachusetts, United States, 02215
Contact: Justin Sun    617-975-7463    Jsun7@bidmc.harvard.edu   
Contact: Sam Booth    617-975-7433    Sbooth1@bidmc.harvard.edu   
Principal Investigator: Bruno Bockorny, MD         
DF/HCC Recruiting
Boston, Massachusetts, United States, 02215
Contact: Alexandra Bird       Alexandra_Bird@DFCI.HARVARD.EDU   
Contact: Michele Vincitore    617-632-3125    Michele_Vincitore@dfci.harvard.edu   
Principal Investigator: Brian Wolpin, MD         
United States, Michigan
Karmanos Cancer Center, Wayne State University Recruiting
Detroit, Michigan, United States, 48201
Contact: Veronica Gorden    313-576-8271    gordenv@karmanos.org   
Principal Investigator: Philip Philip, MD         
United States, Missouri
Washington University of St Louis Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Atlantic Medical Group Not yet recruiting
Morristown, New Jersey, United States, 07962
Contact: Barbara Peloquin    973-971-6298    barbara.peloquin@atlantichealth.org   
Principal Investigator: Angela Alistar, MD         
Sub-Investigator: Eric D. Whitman, MD         
United States, New York
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Jennifer Tiao    929-455-2437    Jennifer.tiao@nyulangone.org   
Principal Investigator: Paul Oberstein, MD         
Cornell Medical College Recruiting
New York, New York, United States
Contact: Navjot Kaur    646-962-9350    nak2028@med.cornell.edu   
Principal Investigator: Manish A. Shah, MD         
University of Rochester Recruiting
Rochester, New York, United States, 14642
Contact: Chris E. LeFeber    585-275-0407    Chris_LeFeber@urmc.rochester.edu   
Principal Investigator: Aram Hezel, MD         
United States, Texas
Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Stephanie Preston    214-370-1282    stephanie.preston@usoncology.com   
Principal Investigator: Carlos Becerra, MD         
United States, Washington
Virginia Mason Medical Center Recruiting
Seattle, Washington, United States, 98101
Contact: Sofia Giacosa    206-287-6282    Sofia.giacosa@virginiamason.org   
Contact: Anas Najjar    206-287-6271    Anas.najjar@virginiamason.org   
Principal Investigator: Vincent Picozzi, MD         
Israel
Rambam Medical Center Recruiting
Haifa, Israel
Contact: Neri Petel    +972-4-7776745    N_PETEL@rambam.health.gov.il   
Contact: Marina Gurman    +972-4-7776742    m_gurman@rambam.health.gov.il   
Principal Investigator: Valeriya Semenysty, MD         
Shaare Zedek Medical Center Not yet recruiting
Jerusalem, Israel, 91031
Contact: Yair Plesser, MSc    972 2 6555727    yairp@szmc.org.il   
Principal Investigator: Alberto Gabizon, MD         
Rabin Medical Center Recruiting
Petaẖ Tiqwa, Israel
Contact: Yael Finkelshtein       yael.finkelshtein@clalit.org.il   
Principal Investigator: Salomon Stemmer, MD         
Chaim Sheba Medical Center Recruiting
Ramat Gan, Israel
Contact: Ilanit Redinsky    03-5304498    Ilanit.Redinsky@sheba.health.gov.il   
Principal Investigator: Talia Golan, MD         
Sourasky Medical Center Recruiting
Tel Aviv, Israel
Contact: Marina Gurovich    972 (3) 6947568    marinagur@tlvmc.gov.il   
Principal Investigator: Ravit Geva, MD         
Spain
Hospital General Universitario de Elche Recruiting
Alicante, Spain
Contact: Silvia Fernandez       silviafernandezf@gmail.com   
Principal Investigator: Javier Gallego, MD         
Vall d'Hebron Recruiting
Barcelona, Spain, 08035
Contact: Marta Beltran    +34 93 489 4374    mbeltran@vhio.net   
Principal Investigator: Teresa Macarulla, MD         
Gregorio Marañón Hospital Recruiting
Madrid, Spain, 28009
Contact: Fernando Galindo    91.426.90.70      
Principal Investigator: Andres Muñoz, MD         
Hospital Universitario de Fuenlabrada Recruiting
Madrid, Spain, 28942
Contact: Carolina Alonso    (+34) 91 600 65 83    capozo@salud.madrid.org   
Principal Investigator: David Gutierrez, MD         
Hospital Universitario Ramón y Cajal Recruiting
Madrid, Spain
Contact: Ana Arévalo Martínez    91 336 82 63    anamaria.arevalo@salud.madrid.org   
Principal Investigator: Carmen Guillén Ponce, MD         
La Paz Recruiting
Madrid, Spain
Principal Investigator: Jaime Feliu, MD         
Hospitalario Universitario de Ourense Recruiting
Ourense, Spain
Principal Investigator: Mercedes Salgado, MD         
Clinic Universidad de Navarra Recruiting
Pamplona, Spain
Contact: Joana Sofía Reis de Carvalho    948 296 695    jreis@unav.es   
Principal Investigator: Mariano Ponz, MD         
University Hospital of Salamanca Recruiting
Salamanca, Spain
Contact: Aline Rodrigues Françoso, PhD    923.291100 ext 55749    arodrigues@saludcastillayleon.es   
Principal Investigator: Martin Navarro, MD         
Marques de Valdecilla de Santander Recruiting
Santander, Spain
Principal Investigator: Fernando Rivera, MD         
Hospital Universitari i Politècnic La Fe, Recruiting
Valencia, Spain
Principal Investigator: Rob Diaz Beveridge, MD         
Sponsors and Collaborators
BioLineRx, Ltd.
Merck Sharp & Dohme Corp.
Investigators
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Study Chair: Abi Vainstein, MD BioLineRx, Ltd.

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Responsible Party: BioLineRx, Ltd.
ClinicalTrials.gov Identifier: NCT02826486    
Other Study ID Numbers: BL-8040.PAC.201
First Posted: July 11, 2016    Key Record Dates
Last Update Posted: January 3, 2020
Last Verified: January 2020
Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Pembrolizumab
Camptothecin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action