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Trial record 1 of 1 for:    NCT03184558
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Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC

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ClinicalTrials.gov Identifier: NCT03184558
Recruitment Status : Completed
First Posted : June 12, 2017
Last Update Posted : April 3, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
BerGenBio ASA

Tracking Information
First Submitted Date  ICMJE May 30, 2017
First Posted Date  ICMJE June 12, 2017
Last Update Posted Date April 3, 2019
Actual Study Start Date  ICMJE July 26, 2017
Actual Primary Completion Date August 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
Objective Response Rate [ Time Frame: The disease response is the best improvement or change in a patient's cancer burden, as measured from baseline (screening) and then measured again at regular intervals over the whole period of the study, an average of 24 months. ]
Objective Response Rate includes all patients whose cancer has a partial or complete response.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03184558 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 9, 2017)
  • Disease Control Rate [ Time Frame: Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression (worsens) or study completion, an average of 24 months. ]
    Disease Control Rate includes all patients who have a partial or complete response, or who maintain stable disease.
  • Duration of Response [ Time Frame: Disease response is assessed every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or study completion, an average of 24 months. ]
    Duration of Response includes patients with a partial or complete response and is measured from the date of response until the cancer progresses (worsens).
  • Time to Progression [ Time Frame: Disease assessments are conducted at screening and then every 9 weeks for the first 45 weeks and then every 12 weeks until disease progression or death, whichever comes first, up to study completion (an average of 24 months). ]
    Time to Progression is measured from the date of first dose to the date the cancer progresses (worsens) and includes all patients.
  • Overall Survival [ Time Frame: Survival visits are conducted every 12 weeks after disease progression until death or until study completion (an average of 24 months). ]
    Overall Survival is measured from the date of first dose to the date of death or the date the patient is last known to be alive. It includes all patients.
  • Number of patients with Adverse Events (as assessed by CTCAE v4.03) [ Time Frame: Adverse Events are recorded from the date of consent until up to 120 days after cessation of both treatments ]
    The number of patients with each Adverse Event will be summarised.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 9, 2017)
Correlation of Response Rate with baseline biomarkers [ Time Frame: The biomarkers are collected at screening; the response rate is the best improvement or change in a patient's cancer burden, as measured from baseline (screening) and then again at regular intervals, over the whole study (an average of 24 months). ]
Biomarkers (Axl kinase and PD-L1 expression) will be measured at screening using a diagnostic test. The Response Rate will be summarised according to Biomarker status (positive or negative) and includes all patients.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC
Official Title  ICMJE A Phase II, Multi Centre Study of BGB324 in Combination With Pembrolizumab in Patients With Previously Treated, Locally Advanced and Unresectable or Metastatic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)
Brief Summary This is an open label, single arm, multi-centre phase II study to assess the anti-tumour activity and safety of bemcentinib (BGB324) in combination with pembrolizumab in up to 56 patients with previously treated, locally advanced and unresectable, or metastatic TNBC or TN-IBC. The study will utilise an extension of Simon's 2-stage design. The primary objective is objective response rate.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Extension to Simon's 2-stage design allowing termination at the end of Stage 1 for either futility or efficacy.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Triple Negative Breast Cancer
  • Inflammatory Breast Cancer Stage IV
Intervention  ICMJE Drug: Bemcentinib; pembrolizumab
Bemcentinib is a selective Axl kinase inhibitor; pembrolizumab is a PD-1 inhibitor.
Other Name: BGB324; Keytruda
Study Arms  ICMJE Experimental: Bemcentinib (BGB324) + pembrolizumab
Bemcentinib (BGB324) in combination with pembrolizumab. Bemcentinib capsules are administered at 400mg on days 1-3, and 200mg there after. Pembrolizumab is an IV infusion, administered at a dose of 200mg every 3 weeks.
Intervention: Drug: Bemcentinib; pembrolizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 2, 2019)
29
Original Estimated Enrollment  ICMJE
 (submitted: June 9, 2017)
56
Actual Study Completion Date  ICMJE August 30, 2018
Actual Primary Completion Date August 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Provision of signed informed consent.
  2. Male and non-pregnant females who are aged 18 years or older at the time of provision of informed consent.
  3. Histopathologically or cytologically documented TNBC or TN-IBC. Tumors must have been confirmed negative for ER and PR by IHC (<1% positive tumor nuclei, as per ASCO-CAP guideline recommendations) and negative for HER2 by IHC or fluorescent or chromogenic in situ hybridization (FISH or CISH). Patients with equivocal HER2 results by IHC should have their negativity status confirmed by FISH.
  4. Locally advanced and unresectable or metastatic TNBC or triple negative inflammatory breast cancer.
  5. Received one or more prior therapies for TNBC or inflammatory breast cancer in the metastatic setting, and prior treatment (metastatic or (neo) adjuvant) must have included a prior taxane and/or anthracycline-based therapy.
  6. Has measurable disease as defined by RECIST 1.12 on computed tomography (CT) or magnetic resonance imaging (MRI) and 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.
  7. Provision of suitable tumor tissue for the analysis of Axl kinase expression and PD-L1 expression.
  8. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1.
  9. Life expectancy of at least 3 months.
  10. Adequate organ function confirmed at Screening and within 10 days of initiating treatment, as evidenced by:

    • Platelet count ≥100,000 /mm3;
    • Hemoglobin ≥9.0 g/dL (≥5.6 mmol/L);.
    • Absolute neutrophil count (ANC) >1,500 /mm3;
    • Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) ≤2.5 times the upper limit of normal (ULN), or ≤5 times the ULN for patients with liver metastases;
    • Total bilirubin ≤1.5 times the ULN, or direct bilirubin <ULN for patients with total bilirubin levels >1.5xULN;
    • Creatinine ≤1.5 times the ULN and calculated creatinine clearance >60 mL/min (by Cockcroft Gault formula; see Appendix B);
    • International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 times the ULN and Activated Partial Thromboplastin Time (aPTT) ≤1.5 times the ULN. Note: If patient is receiving anticoagulant therapy, then PT or PTT must be within therapeutic range of intended use of anticoagulants;
    • LDH ≤2.5 times the ULN.
  11. Female patients of childbearing potential must have a negative pregnancy test (either urine or serum pregnancy test) within 72 hours prior to the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  12. Have resolution of toxic effect(s) of the most recent prior chemotherapy to Grade 1 or less (except alopecia). If the patient received major surgery or radiation therapy of >30 Gy, they must have recovered from the toxicity and/or complications from the intervention.
  13. Patients of reproductive potential must be willing to practice highly effective methods of contraception throughout the study and for 120 days after the last dose of study medication. Abstinence is acceptable if this is the usual lifestyle of the patient.

Exclusion Criteria:

  1. Has disease that is suitable for local therapy administered with curative intent.
  2. More than 3 previous lines of therapy in the metastatic setting.
  3. Has received prior therapy with an immunomodulatory agent.
  4. Has a known additional malignancy that is progressing or requires active treatment. Note: Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  5. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  6. History of the following cardiac conditions:

    • Congestive cardiac failure of >Grade II severity according to the NYHA;
    • Ischemic cardiac event including myocardial infarction within 3 months prior to first dose;
    • Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension (i.e. sustained systolic BP >160 mmHg or diastolic BP >90 mmHg), or need to change medication due to lack of disease control within 6 weeks prior to the provision of consent;
    • History or presence of sustained bradycardia (≤55 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible;
    • Family history of long QTc syndrome; personal history of long QTc syndrome or previous drug-induced QTc prolongation of at least Grade 3 (QTc >500 ms).
  7. Abnormal left ventricular ejection fraction on echocardiography or MUGA (less than the lower limit of normal for a patient of that age at the treating institution or <45%, whichever is lower).
  8. Current treatment with any agent known to cause Torsades de Pointes which cannot be discontinued at least five half-lives or two weeks prior to the first dose of study treatment.
  9. Screening 12-lead ECG with a measurable QTc interval according to Fridericia's correction >450 ms.
  10. 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 study treatment.
  11. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤Grade 1 or at baseline) from AEs due to a previously administered agent.
  12. Received an anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the first dose of study treatment or who has not recovered (i.e. ≤Grade 1 or baseline) from AEs due to agents administered more than 4 weeks earlier.
  13. Major surgery within 28 days prior to start of study treatment and failure to have recovered adequately from the toxicity and/or complications from the intervention prior to the first dose of study treatment.
  14. 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 4 weeks prior to the first dose of study treatment.
  15. 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 study treatment.
  16. Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
  17. Known history of human immunodeficiency virus (HIV 1/2 antibodies)
  18. Has known active infection with Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA (qualitative) is detected).
  19. Has received a live-virus vaccination within 30 days of planned treatment start. Note: Seasonal flu vaccines that do not contain live virus are permitted.
  20. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
  21. Has a history of interstitial lung disease.
  22. Inability to swallow or tolerate oral medication.
  23. Existing gastrointestinal disease affecting drug absorption such as celiac disease or Crohn's disease, or previous bowel resection which is considered to be clinically significant or could interfere with absorption.
  24. Known lactose intolerance.
  25. Requires vitamin K antagonists. Note: Patients receiving low doses prescribed to maintain the patency of venous access devices may be included. Factor Xa antagonists are permitted.
  26. Treatment with any of the following: histamine receptor 2 inhibitors, proton pump inhibitors or antacids within 7 days of start of study treatment.
  27. Treatment with any medication which is predominantly metabolized by CYP3A4 and has a narrow therapeutic index.
  28. Known hypersensitivity to bemcentinib, pembrolizumab, or any of their excipients.
  29. Has an active infection requiring systemic therapy (apart from cutaneous infections).
  30. Has a history or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the Investigator, might confound the results of the trial, interfere with the patient's participation and compliance in the trial, or means it is not in the best interests of the patient to participate.
  31. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting from Screening through to 120 days after the last dose of study treatment.
  32. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Norway,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03184558
Other Study ID Numbers  ICMJE BGBC007
MK-3475 PN530 ( Other Identifier: MSD )
2016-003608-30 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party BerGenBio ASA
Study Sponsor  ICMJE BerGenBio ASA
Collaborators  ICMJE Merck Sharp & Dohme Corp.
Investigators  ICMJE Not Provided
PRS Account BerGenBio ASA
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP