Safety and effect of BL-8040 with pembrolizumab in patients with pancreatic cancer
- Conditions
- Pancreatic cancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-004372-36-ES
- Lead Sponsor
- BioLineRx Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 80
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 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.Previous treatment lines
a.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.
b.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
a.Hematological:
•White blood cell (WBC) = 2,500/mm^3
•Absolute neutrophil count
oCohort 1: = 1000 /mm^3
oCohort 2: = 1500 /mm^3
•Platelet count = 100,000/mm^3
•Hemoglobin =9 g/dL or =5.6 mmol/L
•Hematocrit =30%
b.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
c.Hepatic function:
•Total Bilirubin: within institutional normal ranges
•Aspartate aminotransferase/ serum glutamic oxaloacetic transaminase (AST/SGOT) and Alanine amino transferase/ serum glutamate-pyruvate transaminase (ALT/SGPT): =2.5xULN OR =5xULN for subjects with liver metastases
d.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:
a.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
•Amenorr
1. 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. Active infection requiring systemic therapy or uncontrolled infection.
4. 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. An underlying medical condition that precludes study participation.
6. Has a disease that is suitable for therapy administered with curative intent.
7. Currently participating and receiving study therapy or has participated in a study of an investigational agent or device and received study therapy within 4 weeks of the first dose of treatment.
8. Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of the study.
9. 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. 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 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) is not considered a form of systemic treatment and is allowed.
12. Received transfusions of blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to study Day 1.
13.History of (non-infectious) pneumonitis that required steroids or current pneumonitis.
14. History of interstitial lung disease.
15. O2 saturation < 92% (on room air).
16. For both Cohorts: 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: ventricular arrhythmias or uncontrolled blood pressure, or severe arterial thromboembolic events less than 6 months prior to study initiation.
17. History or current evidence of any condition, therapy, or laboratory abnormality that might confound study results, interfere with the subject’s participation for the duration of the trial, or is not in the best interest of the subject in the opinion of the treating Investigator.
18. Known psychiatric or substance abuse disorders that would interfere with cooperation with study requirements.
19. 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. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or previously particip
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method