A Phase III, Randomized, Double-blind Study to Evaluate Chemotherapy plus Pembrolizumab vs Chemotherapy plus Placebo as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)

• Register: EUCTR
• Last refreshed on: 3 April 2017
• Main ID: EUCTR2016-004740-11-FR
• Date of registration: 30/03/2017
• Prospective Registration: No
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
• Public title: A Phase III, Randomized, Double-blind Study to Evaluate Chemotherapy plus Pembrolizumab vs Chemotherapy plus Placebo as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC)
• Scientific title: A Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab plus Chemotherapy vs Placebo plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for Triple Negative Breast Cancer (TNBC) - Evaluate chemotherapy plus MK-3475 vs chemotherapy plus placebo and MK-3475 vs placebo for TNBC
• Date of first enrolment: 23/03/2017
• Target sample size: 855
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004740-11
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Australia, Brazil, Canada, Colombia, France, Germany, Ireland, Israel, Italy, Japan, Korea, Republic of, Poland, Portugal, Russian Federation, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Contacts

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

• Name: Global Clinical Trial Operations
• Affiliation: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
2.Be a male or female subject >18 years of age on day of signing informed consent.
3.Have centrally confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
4.Have previously untreated locally advanced non-metastatic (M0) TNBC defined as the following combined primary tumor (T) and regional lymph node (N) staging per AJCC for breast cancer staging criteria version 7 as assessed by the investigator based on radiological and/or clinical assessment: T1c, N1-N2, T2, N0-N2, T3, N0-N2,T4a-d, N0-N2
5.Provide a core needle biopsy consisting of at least 2 separate tumor cores from the primary tumor at screening to the central laboratory.
6.Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 10 days of treatment initiation.
7.Demonstrate adequate organ function as defined in the protocol. All screening labs should be performed within 10 days of treatment initiation.
8.Have left ventricular ejection fraction (LVEF) of =50% or = institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening.
9.Males and female subjects of childbearing potential must be willing to use an adequate method of contraception. Contraception, for the course of the study through 12 months after the last dose of study medication for subjects who have received cyclophosphamide, and 6 months after the last dose of study medication for subjects who did not.
10.(Female subject of childbearing potential) Have a negative urine or serum p regnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or borderline a serum pregnancy test will be required.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 55

Exclusion criteria:
1.Has a history of invasive malignancy =5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
2. Has received prior chemotherapy, targeted therapy, and radiation therapy within the past 12 months.
3. 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 MK-3475 clinical trials.
4. Is currently participating in or has participated in an interventional clinical trial with an investigational compound or device within 4 weeks of the first dose of treatment in this current trial.
5.Has received a live vaccine within 30 days of the first dose of study treatment.
6.Has an active autoimmune disease that has required systemic treatment in 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) is not considered a form of systemic treatment.
7. 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 trial treatment.
8. Has a known history of Human Immunodeficiency Virus (HIV) (HIV
1/2 antibodies).
9. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
10. Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
11. Has an active infection requiring systemic therapy.
12.Has significant cardiovascular disease, such as:
a) History of myocardial infarction, acute coronary syndrome or coronary
angioplasty/stenting/bypass grafting within the last 6 months
b) Congestive heart failure (CHF) New York Heart Association (NYHA) Class II-IV or history of CHF NYHA class III or IV
13. Has a history or current evidence of any condition, therapy, lab abnormality or other circumstance that might expose the subject to risk by participating in the trial, confound the results of the trial, or interfere with the subject’s participation for the full duration of the trial.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
15. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 12 months after the last dose of trial treatment for subjects who have received cyclophosphamide, and for 6 months after the last dose of study medication for subjects who have not.
16. Has a known hypersensitivity to the components of the study therapy or its analogs.
17. Has a known history of active TB (Bacillus Tuberculosis)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Neoadjuvant and adjuvant treatment for locally-advanced TNBC
MedDRA version: 19.1 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

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 name: Anti-PD-1 monoclonal antibody
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Secondary Objective: 1.To evaluate the rate of pCR using an alternative definition, ypT0 ypN0 as assessed by the local pathologist at the time of definitive surgery in subjects with locally advanced TNBC.
2.To evaluate the rate of pCR using the definition of (ypT0/Tis ypN0) as assessed by the local pathologist at the time of definitive surgery in individuals with programmed death - ligand 1 (PD-L1) (+) tumors.
3.To evaluate the EFS as assessed by Investigator in individuals with
PD-L1 (+) tumors during the Neoadjuvant and Adjuvant Treatment Phases.
4.To evaluate the rate of pCR using an alternative definition, ypT0 ypN0 as assessed by the local pathologist at the time of definitive surgery in individuals with PD-L1 (+) tumors.
5.To evaluate the rate of pCR using an alternative definition, ypT0/Tis as assessed by the local pathologist at the time of definitive surgery in subjects with locally advanced TNBC and in individuals with PD-L1 (+) tumors.
Refer to protocol for objectives 6 and 7

Timepoint(s) of evaluation of this end point: After Definitive Surgery and at any point PD/Recurrance occurs

Main Objective: 1. To evaluate the rate of pCR using the definition of ypT0/Tis ypN0 (i.e.,
no invasive residual in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist at the time of definitive surgery in subjects with locally advanced TNBC
2.To evaluate the event-free survival (EFS) as assessed by Investigator in subjects with locally advanced TNBC during the Neoadjuvant and Adjuvant Treatment Phases.

Primary end point(s): 1.Pathological complete response rate (ypT0/Tis ypN0) in subjects with locally advanced TNBC.
2. Event-free survival (EFS) in subjects with locally advanced TNBC.

Secondary Outcome(s)

Secondary end point(s): Pathological complete response rate (ypT0 ypN0) in subjects with locally advanced TNBC.

Timepoint(s) of evaluation of this end point: After Definitive Surgery, any point PD/Recurrance occurs, overall survival (time of death)

Secondary ID(s)

2016-004740-11-PT

MK-3475-522

Source(s) of Monetary Support

Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.