Clinical Trials /

Bemcentinib (BGB324) in Combination With Pembrolizumab in Patients With TNBC

NCT03184558

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Completed

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: BGB324 in Combination With Pembrolizumab in Patients With TNBC
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: BGBC007
  • SECONDARY ID: MK-3475 PN530
  • SECONDARY ID: 2016-003608-30
  • NCT ID: NCT03184558

Conditions

  • Triple Negative Breast Cancer
  • Inflammatory Breast Cancer Stage IV

Interventions

DrugSynonymsArms
BGB324; pembrolizumabKeytrudaBGB324 + pembrolizumab

Purpose

This is an open label, single arm, multi-centre phase II study to assess the anti-tumour activity and safety of 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.

Trial Arms

NameTypeDescriptionInterventions
BGB324 + pembrolizumabExperimentalBGB324 in combination with pembrolizumab. BGB324 capsules are administered at 400mg on days1-3, and 200mg there after. Pembrolizumab is an IV infusion, administered at a dose of 200mg every 3 weeks.
  • BGB324; pembrolizumab

Eligibility Criteria

        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 BGB324, 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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.
Safety Issue:
Description:Objective Response Rate includes all patients whose cancer has a partial or complete response.

Secondary Outcome Measures

Measure: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.
Safety Issue:
Description:Disease Control Rate includes all patients who have a partial or complete response, or who maintain stable disease.
Measure: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.
Safety Issue:
Description:Duration of Response includes patients with a partial or complete response and is measured from the date of response until the cancer progresses (worsens).
Measure: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).
Safety Issue:
Description:Time to Progression is measured from the date of first dose to the date the cancer progresses (worsens) and includes all patients.
Measure: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).
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description:The number of patients with each Adverse Event will be summarised.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:BerGenBio ASA

Trial Keywords

  • BGB324
  • TNBC
  • pembrolizumab
  • Keytruda

Last Updated

June 9, 2017