Previously Treated, Locally Advanced and Unresectable or Metastatic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)
Conditions
Interventions
Product Name: BGB324
Product Code: BGB324
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: BGB324
CAS Number: 1037624-75-1
Sponsors
BerGenBio ASA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of signed informed consent. 2. Age 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 (1,500 /mm3; d. 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; e. Total bilirubin =1.5 times the ULN, or direct bilirubin 1.5xULN; f. Creatinine =1.5 times the ULN and calculated creatinine clearance >60 mL/min (by Cockcroft Gault formula; see Appendix B); g. 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; h. 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
Exclusion criteria
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. 5. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. 6. History of the following cardiac conditions: a. Congestive cardiac failure of >Grade II severity according to the NYHA b. Ischemic cardiac event including myocardial infarction within 3 months prior to first dose; c. Uncontrolled cardiac disease, including unstable angina, uncontrolled hypertension or need to change medication due to lack of disease control within 6 weeks prior to the provision of consent; d. History or presence of sustained bradycardia (=55 BPM), left bundle branch block, cardiac pacemaker or ventricular arrhythmia. e. 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 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 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 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess anti-tumor activity of the combination of BGB324 and pembrolizumab ; Secondary Objective: To assess the safety of BGB324 and pembrolizumab when given in combination To further assess the anti-tumor activity of the combination of BGB324 and pembrolizumab The number and frequency of adverse events; assessment of safety laboratory parameters, vital signs and ECGs ;Primary end point(s): Objective Response Rate; Timepoint(s) of evaluation of this end point: The study will utilize a 2-stage, single arm, extension of Simon’s 2-stage design1 with one (efficacy) interim and a final analysis. The interim analysis will be conducted when 28 patients are evaluable for Objective Response Rate (ORR). Recruitment to the study will be halted once 28 evaluable patients have been entered and whilst the Stage 1 interim analysis is conducted. Recruitment will recommence if the decision is made to continue to the maximum of 56 evaluable patients. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Duration of Response Disease Control Rate Time to progression Survival at 12 months Response by Biomarker expression Safety ; Timepoint(s) of evaluation of this end point: The study will utilize a 2-stage, single arm, extension of Simon’s 2-stage design1 with one (efficacy) interim and a final analysis. The interim analysis will be conducted when 28 patients are evaluable for Objective Response Rate (ORR). Recruitment to the study will be halted once 28 evaluable patients have been entered and whilst the Stage 1 interim analysis is conducted. Recruitment will recommence if the decision is made to continue to the maximum of 56 evaluable patients. | — |
Countries
Norway, Spain, United Kingdom, United States
Contacts
Public ContactClinical Project Manager
BerGenBio ASA
Outcome results
None listed