A Phase II Multi Center Study of BGB324 in Combination with Pembrolizumab in Patients with Previously Treated Advanced Adenocarcinoma of the Lung
- Conditions
- Previously Treated Advanced Adenocarcinoma of the LungTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-003609-32-ES
- Lead Sponsor
- BerGenBio AS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 48
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 Stage IV adenocarcinoma non-small cell lung cancer (NSCLC). Note: Patients with a mixed histology including a significant area of adenocarcinoma histology are eligible.
4.Has disease progression on or after a prior platinum-containing chemotherapy. Note: Patients with Epidermal growth factor receptor (EGFR) mutations or ALK genomic rearrangements must have documented disease progression on at least one licensed therapy for these indications.
5.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.
6.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.
7.Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1 [Appendix A].
8.Life expectancy of at least 3 months.
9.Adequate organ function confirmed at Screening within 10 days of treatment initiation - 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.
f.Creatinine =1.5 times the ULN or 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 Partial thromboplastin time (PTT) must be within therapeutic range of intended use of anticoagulants;
10.Female patients of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to the first dose of study treatment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
11.Patients (both male and female) of reproductive potential must be willing to practice highly effective methods of contraception (such as those described in Section 6.13) throughout the study and for 120 days after the last dose of study medication. Abstinence is acceptable if this is the usual lifestyle for the patient. Female patients are considered NOT of childbearing potential if they have a history of surgical sterility or evidence of post-menopausal status defined as any of the following:
a.=45 years of age and has not had menses for more than 1 year;
b.Amenorrheic for >2 years without a hysterectomy and oophorectomy and a follicle stimulating hormone (FSH) value in the postmenopausal range upon Screening evaluation;
c.Post hysterectomy, oophorectomy or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasou
1.Has disease suitable for local therapy administered with curative intent.
2.Has received more than 1 prior line of chemotherapy for advanced or metastatic adenocarcinoma of the lung.
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 (Appendix C: defined as symptomatic at less than ordinary levels of activity).
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. Note: Patients with a supraventricular arrhythmia requiring medical treatment, but with a normal ventricular rate are eligible.
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 >500ms).
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-lifes 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.Received chemotherapy or targeted small molecule therapy or radiation therapy within 2 weeks prior to starting study treatment or who has not recovered (i.e. =Grade 1 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 or administration of colony stimulating factors .
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
17.Known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies).
18.Has known active infection with Hepatitis B or Hepatitis C
19.Has received a live-virus vaccination within 30 days of planned treatment start.
20.Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
21.Has a history of interstitial lung disease.
22.Existing gastrointestinal disease affecting drug absorption s
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