A Phase II, Multi Center Study of BGB324 in combination with Pembrolizumab in Patients with Previously Treated, Locally Advanced and Unresectable or Mestastic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)
- Conditions
- Previously Treated, Locally Advanced and Unresectable or Metastatic Triple Negative Breast Cancer (TNBC) or Triple Negative Inflammatory Breast Cancer (TN-IBC)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003608-30-GB
- Lead Sponsor
- BerGenBio ASA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 56
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% positive tumor nuclei, as
per ASCO-CAP guideline recommendations3) 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 TN-IBC, which may include
adjuvant, neo-adjuvant and metastatic therapy, and 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. Suitable tumor tissue must consist of a minimum of newly acquired (fresh)
tumor tissue sample (as a FFPE block), together with either further newly acquired
tumor tissue (i.e. further FFPE block) or an archival tumor tissue sample (as a further
FFPE block or further 10 unstained slides). See Section 5.3.13 for further details.
8. Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 [Appendix
A].
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:
a. Platelet count =100,000 /mm3;
b. Hemoglobin =9.0 g/dL (=5.6 mmol/L);
c. Absolute neutrophil count (ANC) >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 total bilirubin levels >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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method