Study Assessing Safety and Efficacy of Combination of BL-8040 and Pembrolizumab in Metastatic Pancreatic Cancer Patients

NCT02826486 | Completed Phase 2 Results DMC

• 1 other identifier: BL-8040.PAC.201
• Study Type: interventional
• Target: 80
• Locations: 4 countries
• Sites: 31

Brief 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.

Conditions

Metastatic Pancreatic Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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)

  Through study completion, an average of 2 years

• Disease Control (DC)

  Through study completion, an average of 2 years

Study Arms (2)

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

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.

Drug: BL-8040; Drug: Pembrolizumab; Drug: Chemotherapy

Interventions

BL-8040 DRUG

BL-8040 subcutaneous (SC) injections

BL-8040 + Pembrolizumab + Chemotherapy; Cohort 1: BL-8040 + Pembrolizumab (Keytruda®)

Pembrolizumab DRUG

Pembrolizumab will be given as a 30-minute IV infusion

Also known as: Keytruda

BL-8040 + Pembrolizumab + Chemotherapy; Cohort 1: BL-8040 + Pembrolizumab (Keytruda®)

Chemotherapy DRUG

• IV Onivyde® followed by IV leucovorin (LV), followed by IV fluorouracil (5-FU), every 2 weeks.

Also known as: Onivyde / Leucovorin (LV) / Fluorouracil (5-FU)

BL-8040 + Pembrolizumab + Chemotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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).

Sponsors & Collaborators

• BioLineRx, Ltd.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (31)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Honor Health

Scottsdale, Arizona, 85258, United States

Location

Ochsner Medical Center

New Orleans, Louisiana, 70121, United States

Location

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center (BIDMAC)

Boston, Massachusetts, 02215, United States

Location

DF/HCC

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Center, Wayne State University

Detroit, Michigan, 48201, United States

Location

Washington University of St Louis

St Louis, Missouri, 63110, United States

Location

Atlantic Medical Group

Morristown, New Jersey, 07962, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Cornell Medical College

New York, New York, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

Rambam Medical Center

Haifa, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

Rabin Medical Center

Petah Tikva, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, Israel

Location

Sourasky Medical Center

Tel Aviv, Israel

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital General Universitario de Elche

Alicante, Spain

Location

Vall d'Hebron

Barcelona, 08035, Spain

Location

Gregorio Marañón Hospital

Madrid, 28009, Spain

Location

Hospital Universitario de Fuenlabrada

Madrid, 28942, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, Spain

Location

La Paz

Madrid, Spain

Location

Hospitalario Universitario de Ourense

Ourense, Spain

Location

Clinic Universidad de Navarra

Pamplona, Spain

Location

University Hospital of Salamanca

Salamanca, Spain

Location

Marques de Valdecilla de Santander

Santander, Spain

Location

Hospital Universitari i Politècnic La Fe,

Valencia, Spain

Location

Related Publications (1)

• 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.

  PMID: 32451495 DERIVED

MeSH Terms

Interventions

4-fluorobenzoyl-TN-14003; pembrolizumab; Drug Therapy; irinotecan sucrosofate; Leucovorin; Fluorouracil

Intervention Hierarchy (Ancestors)

Therapeutics; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: VP Clinical & Medical Affairs
• Organization: BioLineRx Ltd

clinicaltrials@biolinerx.com

+972-8-642-9100

Study Officials

• Abi Vainstein, MD

  BioLineRx, Ltd.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2016
• First Posted: July 11, 2016
• Study Start: September 1, 2016
• Primary Completion: September 6, 2022
• Study Completion: September 6, 2022
• Last Updated: August 28, 2024
• Results First Posted: August 28, 2024

Record last verified: 2024-08

Locations

IL (5); ES (11); KR (1); US (14)