Patients with HER2-negative advanced breast cancer. MedDRA version: 19.0 Level: LLT Classification code 10072737 Term: Advanced breast cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: Pembrolizumab
Product Code: MK-3475
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PEMBROLIZUMAB
CAS Number: 1374853-91-4
Current Sponsor code: MK-3475
Other descriptive
Sponsors
GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The patient has signed and dated the informed consent document and it has been obtained before conducting any procedure specifically for the study. 2. Female = 18 years of age on day of signing informed consent. 3. Histological/cytological confirmation of breast cancer with evidence of advanced disease, not amenable to resection or radiation therapy with curative intent. 4. Documented luminal A, luminal B (HER2-negative) or triple negative disease by immunohistochemistry (IHQ) and/or in situ hybridization (FISH/CISH/SISH) based on local testing on the most recent tumour biopsy defined as follows: o Luminal A: tumour with positive oestrogen receptor (ER) status (>1% of tumour cells with ER expression) and HER2-negative status (IHQ score 0/1+ or negative by in situ hybridization defined as a HER2/CEP17 ratio 20% of tumour cells with PgR expression) and low Ki67 (1% of tumour cells with ER expression) and HER2-negative status (IHQ score 0/1+ or negative by in situ hybridization defined as a HER2/CEP17 ratio 1.5 x ULN o Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT) = 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Activated Partial Thromboplastin Time (aPTT) = 1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. 8. Prior treatment with anthracyclines and taxanes (unless clinically contraindicated) and two or more prior lines of hormone therapy in hormone receptor positive disease. 9. At least 3 months life expectancy. 10. Patient of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study drug/medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 11. Patients of childbearing potential (see section 4.4. for definition) must be willing to use an adequate method of
Exclusion criteria
Exclusion criteria: 1. HER2-positive disease by immunohistochemistry or in situ hybridation (FISH-SISHCISH). 2. Patient is currently participating 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 drug/medication. 3. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study day 1 or who has not recovered (i.e., = grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier. 4. 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 adverse events due to a previously administered agent. o Note: Patients with = grade 2 neuropathy are an exception to this criterion and may qualify for the study. o Note: If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. 5. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. 6. Has received a live vaccine within 30 days of planned start of study therapy. o Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however, intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed. 7. Has hypersensitivity to pembrolizumab, gemcitabine or any of theirs excipients. 8. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and all neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability. 9. 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 drug/medication. 10. 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). 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. 11. Has a current or prior malignancy within the previous 5 years (other than breast cancer or adequately treated basal cell or squamous cell carcinoma of the skin or in-situ carcinoma of the cervix). 12. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis. 13. Has an active infection requiring systemic therapy. 14. Has a known history of active TB (Bacillus Tuberculosis) or Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or a known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). 15. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Run-in-phase: To determine the Recommended Phase II Dose (RP2D) of gemcitabine in combination with fixed doses of pembrolizumab. · Phase II: To assess the efficacy of pembrolizumab in combination with gemcitabine in terms of Objective Response Rate (ORR) in patients with HER2-negative ABC.;Secondary Objective: The following secondary objectives will be studied: · To assess other efficacy measures of the combination in patients included in the phase II (including those in the run-in-phase at the same dose that in the phase II). · To determine safety and tolerability of the combination in all patients included in the study.;Primary end point(s): Run-in-phase: To determine the incidence rate of Dose Limiting Toxicity (DLT) within the first cycle of the combination. Phase II: Objective Response Rate (ORR) is defined as Complete Response (CR) plus Partial Response (PR) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1.;Timepoint(s) of evaluation of this end point: This study will be considered complete following the data cut-off date and datalock for the final analysis. The data cut-off date for the final analysis will occur after all enrolled patients have died or withdraw of the informed consent or there is sufficient data to achieve the primary nd secondary objectives, whatever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): · Efficacy: - Progression-Free Survival (PFS) assessed according to RECIST version 1.1 by the investigator. - Clinical Benefit Rate (CBR) defined as Complete Response (CR) plus Partial Response (PR) plus Stable Disease (SD) lasting = 24 weeks according to RECIST version 1.1. - Response Duration (RD) assessed according to RECIST version 1.1. - Overall Survival (OS). With special interest on long term responders (i.e. alive at 24 months). · Safety will be assessed by standard clinical and laboratory tests (haematology, serum chemistry). Adverse Events (AE) grade will be defined by the NCI CTCAE (National Cancer Institute Common Terminology Criteria for Adverse Events) version 4.0.;Timepoint(s) of evaluation of this end point: This study will be considered complete following the data cut-off date and datalock for the final analysis. The data cut-off date for the final analysis will occur after all enrolled patients have died or withdraw of the informed consent or there is sufficient data to achieve the primary nd secondary objectives, whatever occurs first. | — |
Countries
Spain
Contacts
Public ContactClinical Operations Department
GEICAM (Fundación Grupo Español de Investigación en Cáncer de Mama)
Outcome results
None listed