Clinical Trials /

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

NCT02826486

Description:

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.

Related Conditions:
  • Pancreatic Adenocarcinoma
  • Pancreatic Intraductal Papillary-Mucinous Neoplasm
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients (COMBAT/KEYNOTE-202)
  • Official Title: A Phase II, Multicenter, Open-label Single Arm Study to Assess the Safety and Efficacy of the Combination of BL-8040 and Pembrolizumab in Patients With Metastatic Pancreatic Cancer, the COMBAT Study

Clinical Trial IDs

  • ORG STUDY ID: BL-8040.PAC.201
  • NCT ID: NCT02826486

Conditions

  • Metastatic Pancreatic Adenocarcinoma

Interventions

DrugSynonymsArms
BL-8040BL-8040 plus pembrolizumab (Keytruda®)
BL-8040 plus pembrolizumabBL-8040 plus keytrudaBL-8040 plus pembrolizumab (Keytruda®)

Purpose

This study will assess the efficacy and safety of BL-8040 as a single agent and in combination with pembrolizumab (Keytruda®) in subjects with metastatic pancreatic adenocarcinoma.

Detailed Description

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

      The study will include 30 subjects with unresectable metastatic pancreatic adenocarcinoma.

      The study consists of two periods:

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

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

      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
      (1.25 mg/kg) three times a week (TIW) and pembrolizumab (200mg) once every three weeks. The
      combination therapy will continue for up to two years, or until progression, clinical
      deterioration or early termination, whichever comes first.
    

Trial Arms

NameTypeDescriptionInterventions
BL-8040 plus pembrolizumab (Keytruda®)ExperimentalBL-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 repeated 3 week long cycles of 200 mg pembrolizumab administered by intravenous infusion (IV) on day 1 of each cycle plus SC injections of BL-8040 1.25 mg/kg three times a week on non-consecutive days.
  • BL-8040
  • BL-8040 plus pembrolizumab

Eligibility 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 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. Subjects with one or more prior treatments for their pancreatic cancer.

          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:

                    -  WBC ≥ 2,500/mm^3

                    -  Absolute neutrophil count ≥ 1000 /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 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 subjects with creatinine levels > 1.5x institutional ULN

               3. Hepatic function:

                    -  Total Bilirubin: ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total
                       bilirubin levels >1.5xULN

                    -  AST (SGOT) and 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

                    -  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

                    -  Amenorrheic 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 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. Has an active infection requiring systemic therapy or uncontrolled infection.

          3. 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.

          4. Has an Underlying medical condition that would preclude study participation.

          5. Has a disease that is suitable for therapy administered with curative intent.

          6. 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.

          7. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
             other form of immunosuppressive therapy within seven days prior to the first dose of
             trial treatment. The use of physiologic doses of corticosteroids may be approved
             after consultation with the Sponsor.

          8. Has had a prior anti-cancer monoclonal antibody within 4 weeks prior to study Day 1
             or who has not recovered (i.e., ≤ Grade 1 or at baseline) from AEs due to agents
             administered more than 4 weeks earlier.

          9. 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 AEs due to a previously administered agent .

         10. An active autoimmune disease that has required systemic treatment in the two years
             preceding the study (i.e. with the 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.

         11. Has received transfusion of blood products (including platelets or red blood cells)
             or administration of colony stimulating factors (including G-CSF, GM-CSF or
             recombinant erythropoetin) within four weeks prior to study Day 1.

         12. Has a history of (non-infectious) pneumonitis that required steroids or current
             pneumonitis.

         13. Has a history of interstitial lung disease.

         14. O2 saturation < 92% (on room air).

         15. 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.

         16. Has known psychiatric or substance abuse disorders that would interfere with
             cooperation with the requirements of the trial.

         17. 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.

         18. 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.

         19. Has a known history of HIV (HIV 1/2 antibodies).

         20. Has known active Hepatitis B (e.g., Hepatitis B Surface Antigen [HBsAg] reactive) or
             Hepatitis C (e.g., Hepatitis C Virus [HCV] RNA [qualitative] is detected).

         21. Has known history of Chronic Hepatitis B or C

         22. 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.

         23. 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 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 7 days prior to trial treatment. This
             exception does not include carcinomatous meningitis which is excluded regardless of
             clinical stability.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:response is determined by assessment of target lesions identified in CT or MRI imaging

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:repeat imaging will be done for confirmation of initial progressive disease
Measure:Overall survival
Time Frame:Through study completion, an average of 2 years, and follow-up until date of death up to 100 weeks.
Safety Issue:
Description:
Measure:Progression-free survival (PFS) by imaging (RECIST 1.1)
Time Frame:through study completion, an average of 2 years
Safety Issue:
Description:imaging will be assessed according to RECIST 1.1
Measure:Progression-free survival (PFS) by imaging (irRECIST)
Time Frame:through study completion, an average of 2 years
Safety Issue:
Description:imaging will be assessed according to irRECIST
Measure:Duration of response
Time Frame:through study completion, an average of 2 years, and follow-up until the date of progression up to 100 weeks.
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:BioLineRx, Ltd.

Last Updated

February 19, 2017