Details
Description
Inclusion Criteria
Exclusion Criteria
Details
Title A Randomized Open-Label Phase III Study of Single Agent Pembrolizumab versus Single Agent Chemotherapy per Physician’s Choice for Metastatic Triple Negative Breast Cancer (mTNBC) – (KEYNOTE 119)
IRB MRK 1115
CC 051608C
Hospital Main Campus
Stage Advanced/Metastatic
Phase Phase 3
Disease Breast
Drug Pembrolizumab
Description
Primary Objectives- To compare progression-free survival (PFS) based on RECIST 1.1 as assessed by blinded central imaging vendor in subjects with PD-L1 positive tumors by blinded central imaging vendor compared to TPC in subjects with PD-L1 positive tumors.
- To compare PFS based on RECIST 1.1 as assessed by blinded central imaging vendor in all subjects
- To compare overall survival (OS) in subjects with PD-L1 positive tumors.
- To compare OS in all subjects.
- To compare overall response rate (ORR), duration of response (DOR), and disease control rate (DCR) based on RECIST 1.1 as assessed by blinded central imaging vendor in subjects with PD-L1 positive tumors and in all subjects.
- To determine the safety and tolerability of pembrolizumab.
- To compare PFS, ORR, DOR, and DCR based on irRECIST as assessed by blinded central imaging review in subjects with PD-L1 positive tumors and in all subjects.
- To evaluate changes in health-related quality-of-life assessments from baseline in subjects with PD-L1 positive tumors and in all subjects using the EORTC QLQ-C30 and QLQ-BR23.
- To characterize utilities in subjects with PD-L1 positive tumors and in all subjects using EuroQol (EQ)-5D.
- To investigate the association between antitumor activity of pembrolizumab in mTNBC and efficacy/resistance biomarkers, utilizing tumor and blood specimens obtained before/during treatment and at disease progression.
- To explore the relationship between genetic variation and response to the treatment(s) administered. Variation across the human genome will be analyzed for association with clinical data collected in this study.
Inclusion Criteria
- Have signed informed consent.
- Be≥18 years of age on day of signing informed consent.
- Have received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on the most recent therapy.
- Have been previously treated with an anthracycline and/or taxane in the (neo) adjuvant or metastatic setting.
- Have centrally confirmed mTNBC (determined b y a newly obtained core or excisional biopsy from a metastatic, not previously irradiated, tumor lesion).
- Have measurable disease based on RECIST 1.1 as assessed by site investigator and local radiology review.
- Have provided a newly obtained core or excisional biopsy from a metastatic, not previously irradiated, tumor lesion for central determination of triple-negative breast cancer status and PD-L1 biomarker analysis. Adequacy of the biopsy specimen for the above analyses must be confirmed by the central laboratory. Repeat samples may be required if adequate tumor tissue is not provided.
- Note: Subjects for whom fresh tumor biopsies cannot be obtained (e.g. inaccessible tumor site or concern for subject safety) may submit an archived tumor specimen only upon agreement from the Sponsor.Have an ECOG performance status of 0 or 1 assessed within 10 days prior of treatment initiation.
- Demonstrate adequate organ function as defined in Table 2.
- Absolute neutrophil count (ANC) ≥1,500/mcL
- Platelets ≥100,000/mcL
- Hemoglobin ≥9 g/dL or ≥5.6 mmol/L without qualifications
- Creatinine ≤1.5xULN OR
- Calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥30 mL/min for subject with creatinine levels >1.5x institutional ULN
- Serum total bilirubin ≤1.5xULN OR Direct bilirubin ≤ULN for subjects with total bilirubin levels >1.5xULN
- AST (SGOT) and ALT (SGPT) ≤2.5xULN OR ≤ 5 X ULN for subjects with active liver metastases
- Alkaline Phosphatase If > 2.5xULN, then liver fraction should be ≤ 2.5xULN
- Albumin ≥3.0 g/dL
- Lactate Dehydrogenase (LDH) < 2.5xULN
- International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- Activated Partial Thromboplastin Time (aPTT) ≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
- Female subjects of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication and agree to use effective contraception, as defined in Section 5.7.2. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.Male subjects should agree to use an adequate method of contraception starting at randomization through at least 120 days after the last dose of pembrolizumab or TPC, according to local standard of care. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
Exclusion Criteria
- Has participated or is currently participating in a study of an investigational agent/device and has received/is receiving the investigational agent/device within 4 weeks of randomization. Note: A subject who has entered the follow-up phase of an investigational study may participate as long as 4 weeks have elapsed since the last dose of the investigational agent and/or removal of the device.
- Has had monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks of randomization.
- Has had chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks of randomization.
- Has not recovered (i.e., ≤ Grade 1 at baseline) from adverse events due to a previously administered therapy. Note: Subjects with ≤ Grade 2 neuropathy or alopecia of any grade are an exception to this criterion and may qualify for the study. Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the surgery prior to randomization.
- Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of randomization.
- Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, and in situ cervical cancer.
- Has known active brain metastases and/or carcinomatous meningitis. Note: Known brain metastases are considered active, if any of the following criteria is applicable:
- Brain imaging during screening demonstrates progression of existing metastases and/or appearance of new lesions compared to brain imaging performed at least 4 weeks earlier.
- Neurological symptoms attributed to brain metastases have not returned to baseline.
- Steroids were used for brain metastases within 28 days of randomization
- Has active/history of pneumonitis requiring treatment with steroids or active/history of interstitial lung disease.
- Has an active infection requiring systemic therapy.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject�s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment as defined in Section 5.7.2.
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137) or has previously participated in Merck MK-3475 clinical trials.
- Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
- Has a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
- Has received a live vaccine within 30 days of randomization.