Metastatic Pancreatic AdenocarcinomaPhase 2COMBATNCT02826486
Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients
A Phase 2 study testing BL-8040, Pembrolizumab and Chemotherapy in people with Metastatic Pancreatic Adenocarcinoma, run by BioLineRx, Ltd. at 31 sites in 4 countries.
Trial summary
This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL-8040/ Pembrolizumab in combination with liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV) in subjects with metastatic pancreatic adenocarcinoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Pancreatic Adenocarcinoma
- What is being tested?
- BL-8040, Pembrolizumab and Chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 31 sitesin 4 countries
- Study dates
- Sep 2016to 6 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years and older.
- Patients must sign a written informed consent prior to entering the study.
- Histologically confirmed (either previously or newly biopsied) metastatic unresectable pancreatic adenocarcinoma, including with intraductal papillary mucinous neoplasm.
- 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.
- Previous treatment lines
- 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.
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- 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.
- 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
- 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.
- Eastern Cooperative Oncology Group (ECOG) status ≤1.
- Life expectancy of at least 3 months.
- Adequate organ function at Baseline as defined below. All laboratory assessments should be performed within 10 days of treatment initiation
- 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%
- Renal function:
- Creatinine ≤1.5 x 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 >1.5 x institutional ULN
- 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): ≤2.5 x ULN OR ≤5 x ULN for subjects with liver metastases
- Coagulation:
- International Normalized Ratio (INR) or 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
- Subjects must use effective contraception:
- 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
- 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.
Who cannot join
- 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.
- For Cohort 2 only: subjects with a bowel obstruction.
- Has an active infection requiring systemic therapy or has an uncontrolled infection.
- 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.
- Has an underlying medical condition that would preclude study participation.
- Has a disease that is suitable for therapy administered with curative intent.
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- 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.
- 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.
- 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 Event (AE) due to agents administered more than 4 weeks earlier.
- 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 .
- 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.
- 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), Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) or recombinant erythropoietin) within 4 weeks prior to study Day 1.
- Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
- Has a history of interstitial lung disease.
- O2 saturation < 92% (on room air).
- 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.
- 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.
- 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. Women with a positive pregnancy test within 72 hours from Baseline.
- Has received prior therapy with an anti-Programmed Cell Death Protein 1 (PD-1), anti-Programmed Cell Death-Ligand 1 (PD-L1), or anti-(Programmed Cell Death-Ligand 2 (PD-L2) agent or if the subject has previously participated in Merck MK-3475 clinical trials.
- 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.
- 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 Hepatitis C Virus (HCV) antibody test or a positive HCV RNA test at Screening)
- Has known history of Chronic Hepatitis B or C
- 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.
- 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.
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Cohort 2: Has clinical ascites requiring treatment
Trial locations and contacts
31 sites in 4 countries.
31 sites in 4 countries
United States14 sites
Massachusetts General Hospital (MGH)
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center (BIDMAC)
Boston, Massachusetts, 02215
DF/HCC
Boston, Massachusetts, 02215
Baylor Charles A. Sammons Cancer Center
Dallas, Texas, 75246
Karmanos Cancer Center, Wayne State University
Detroit, Michigan, 48201
Atlantic Medical Group
Morristown, New Jersey, 07962
Ochsner Medical Center
New Orleans, Louisiana, 70121
NYU Langone Health
New York, New York, 10016
Cornell Medical College
New York, New York
Mayo Clinic
Phoenix, Arizona, 85054
University of Rochester
Rochester, New York, 14642
Honor Health
Scottsdale, Arizona, 85258
Virginia Mason Medical Center
Seattle, Washington, 98101
Washington University of St Louis
St Louis, Missouri, 63110
Spain11 sites
Hospital General Universitario de Elche
Alicante
Vall d'Hebron
Barcelona, 08035
Gregorio Marañón Hospital
Madrid, 28009
Hospital Universitario de Fuenlabrada
Madrid, 28942
Hospital Universitario Ramón y Cajal
Madrid
La Paz
Madrid
Hospitalario Universitario de Ourense
Ourense
Clinic Universidad de Navarra
Pamplona
University Hospital of Salamanca
Salamanca
Marques de Valdecilla de Santander
Santander
Hospital Universitari i Politècnic La Fe,
Valencia
Israel5 sites
Rambam Medical Center
Haifa
Shaare Zedek Medical Center
Jerusalem, 91031
Rabin Medical Center
Petah Tikva
Chaim Sheba Medical Center
Ramat Gan
Sourasky Medical Center
Tel Aviv
About this study
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 (KEYNOTE-202)
This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL-8040/ Pembrolizumab in combination with liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV) in subjects with metastatic pancreatic adenocarcinoma.
Read the 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. Cohorts will be conducted sequentially (one after the other).
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.
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Being tested
- BL-8040, Pembrolizumab, Chemotherapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BL-8040Drug
BL-8040 subcutaneous (SC) injections
PembrolizumabDrug
Also called Keytruda
Pembrolizumab will be given as a 30-minute IV infusion
ChemotherapyDrug
Also called Onivyde / Leucovorin (LV) / Fluorouracil (5-FU)
- IV Onivyde® followed by IV leucovorin (LV), followed by IV fluorouracil (5-FU), every 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: BL-8040 + Pembrolizumab (Keytruda®) | Experimental | 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 200 mg once every three weeks.
* Beginning on Day 10, BL-8040 three times a week Receives: Drug: BL-8040; Drug: Pembrolizumab |
| BL-8040 + Pembrolizumab + Chemotherapy | Experimental | 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. Receives: Drug: BL-8040; Drug: Pembrolizumab; Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR) Assessed by Imaging According to RECIST 1.1 Criteria
Response is determined by assessment of target lesions identified in CT or MRI imaging.
The ORR is assessed according to RECIST 1.1, defined as the sum of PRs (Partial Responses) and CRs (Complete Responses) determined according to best response RECIST 1.1 criteria.
PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
CR is defined as disappearance of all target lesions.
Measured: 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.
Secondary outcomes (3)
Overall Survival
The length of time elapsed from monotherapy Day 1 to death
Measured: Through study completion, an average of 2 years for cohort of the study, and follow-up until date of death up to 100 weeks.
Progression-free Survival (PFS) by Imaging (RECIST 1.1)
Progression-free Survival (PFS) by imaging (assessed according to RECIST 1.1).
Progression is determined by assessment of target lesions identified in CT or MRI imaging. Progression is defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.
Measured: Through study completion, an average of 2 years
Disease Control (DC)
Sum of Partial Response (PR), Complete Response (CR) and Stable Disease (SD). PR is defined as an at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter.
CR is defined as disappearance of all target lesions. Progressive Disease (PD) is defined as an at least 20% increase in the sum of the longest diameter of target lesions.
SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Measured: Through study completion, an average of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2016 (estimated)
- Study startSep 2016
- Primary completion6 Sep 2022
- Study completion6 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Metastatic Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioLineRx, Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Abi Vainstein, MD, Study chair, BioLineRx, Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02826486
- Sponsor's protocol ID
- BL-8040.PAC.201
- Acronym
- COMBAT
- Status last verified
- Aug 2024
- First submitted
- 21 Jun 2016
- Last updated
- 28 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, Golan T, Geva R, Borad MJ, Pedersen KS, Park JO, Ramirez RA, Abad DG, Feliu J, Munoz A, Ponz-Sarvise M, Peled A, Lustig TM, Bohana-Kashtan O, Shaw SM, Sorani E, Chaney M, Kadosh S, Vainstein Haras A, Von Hoff DD, Hidalgo M. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020 Jun;26(6):878-885. doi: 10.1038/s41591-020-0880-x. Epub 2020 May 25.
PubMed 32451495
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 (KEYNOTE-202)
- ClinicalTrials.gov ID
- NCT02826486
- Acronym / sponsor ID
- COMBAT / BL-8040.PAC.201
- Conditions
- Metastatic Pancreatic Adenocarcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- BioLineRx, Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Sep 2016 (actual)
- Primary completion
- 6 Sep 2022 (actual)
- Study completion
- 6 Sep 2022 (actual)
- First posted
- 11 Jul 2016 (estimated)
- Results
- Posted 28 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess the efficacy and safety of BL-8040 in combination with pembrolizumab (Keytruda®) and BL-8040/ Pembrolizumab in combination with liposomal irinotecan (Onivyde®)/5-fluorouracil/leucovorin (5-FU/LV) in subjects with metastatic pancreatic adenocarcinoma.
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. Cohorts will be conducted sequentially (one after the other).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: BL-8040 + Pembrolizumab (Keytruda®) | Experimental | Drug: BL-8040, Drug: PembrolizumabBL-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 200 mg once every three weeks. * Beginning on Day 10, BL-8040 three times a week |
| BL-8040 + Pembrolizumab + Chemotherapy | Experimental | Drug: BL-8040, Drug: Pembrolizumab, Drug: ChemotherapyBL-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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- 18 years and older.
- Patients must sign a written informed consent prior to entering the study.
- Histologically confirmed (either previously or newly biopsied) metastatic unresectable pancreatic adenocarcinoma, including with intraductal papillary mucinous neoplasm.
- 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.
- Previous treatment lines
Key exclusion criteria (27 listed)
- 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.
- For Cohort 2 only: subjects with a bowel obstruction.
- Has an active infection requiring systemic therapy or has an uncontrolled infection.
- 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.
- Has an underlying medical condition that would preclude study participation.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BL-8040BL-8040 subcutaneous (SC) injections | Drug | BL-8040 + Pembrolizumab + Chemotherapy, Cohort 1: BL-8040 + Pembrolizumab (Keytruda®) |
| PembrolizumabAlso: KeytrudaPembrolizumab will be given as a 30-minute IV infusion | Drug | BL-8040 + Pembrolizumab + Chemotherapy, Cohort 1: BL-8040 + Pembrolizumab (Keytruda®) |
| ChemotherapyAlso: Onivyde / Leucovorin (LV) / Fluorouracil (5-FU)• IV Onivyde® followed by IV leucovorin (LV), followed by IV fluorouracil (5-FU), every 2 weeks. | Drug | BL-8040 + Pembrolizumab + Chemotherapy |
Primary outcome
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. The ORR is assessed according to RECIST 1.1, defined as the sum of PRs (Partial Responses) and CRs (Complete Responses) determined according to best response RECIST 1.1 criteria. PR is defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. CR is defined as disappearance of all target lesions.
3 secondary outcomes
Overall Survival
Time frame: Through study completion, an average of 2 years for cohort of the study, and follow-up until date of death up to 100 weeks.
Progression-free Survival (PFS) by Imaging (RECIST 1.1)
Time frame: Through study completion, an average of 2 years
Disease Control (DC)
Time frame: Through study completion, an average of 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32451495Bockorny B, Semenisty V, Macarulla T, Borazanci E, Wolpin BM, Stemmer SM, Golan T, Geva R, Borad MJ, Pedersen KS, Park JO, Ramirez RA, Abad DG, Feliu J, Munoz A, Ponz-Sarvise M, Peled A, Lustig TM, Bohana-Kashtan O, Shaw SM, Sorani E, Chaney M, Kadosh S, Vainstein Haras A, Von Hoff DD, Hidalgo M. BL-8040, a CXCR4 antagonist, in combination with pembrolizumab and chemotherapy for pancreatic cancer: the COMBAT trial. Nat Med. 2020 Jun;26(6):878-885. doi: 10.1038/s41591-020-0880-x. Epub 2020 May 25.
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RecruitingPhase 2
A Phase 2 Study of VS-7375 in Patients With KRAS G12D-Mutated Pancreatic Cancer
Pancreatic Ductal Adenocarcinoma (PDAC), G12D Mutated KRAS
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Abi Vainstein, MD study chair
BioLineRx, Ltd.
31 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BL-8040, Pembrolizumab and Chemotherapy in people with Metastatic Pancreatic Adenocarcinoma, run by BioLineRx, Ltd. at 31 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 34 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States, Spain, Israel, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02826486, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2024; AzTrials last refreshed its copy on 7 Nov 2026.