A Study of Single Agent Pembrolizumab versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer.

• Register: EUCTR
• Last refreshed on: 23 November 2020
• Main ID: EUCTR2015-001020-27-GB
• Date of registration: 30/09/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc
• Public title: A Study of Single Agent Pembrolizumab versus Single Agent Chemotherapy for Metastatic Triple Negative Breast Cancer.
• Scientific 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) - A Study of Single Agent Pembrolizumab vs Single Agent Chemotherapy for
• Date of first enrolment: 29/02/2016
• Target sample size: 600
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001020-27
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; 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

Argentina, Australia, Belgium, Brazil, Colombia, France, Germany, Guatemala, Hong Kong, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, New Zealand, Peru, Philippines, Poland, Russian Federation, Singapore, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, United Kingdom, United States

Contacts

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

• Name: Global Clinical Trials Operations
• Affiliation: Merck Sharp & Dohme (UK) Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Have signed informed consent.
2. Be equal to or greater than 18 years of age on day of signing informed consent.
3. Have received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on or after their most recent therapy.
4. Have been previously treated with an anthracycline and/or taxane in the (neo)adjuvant or metastatic setting.
5. Have centrally confirmed mTNBC (determined by a newly obtained core or excisional biopsy from a metastatic, not previously irradiated, tumor lesion).
6. Have measurable disease based on RECIST 1.1 as assessed by site Investigator and local radiology review.
7. 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 (eg inaccessible tumor site or concern for subject safety) may submit an archived tumor specimen only upon agreement from the Sponsor.
8. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 10 days prior of treatment initiation.
9. Demonstrate adequate organ function
10. Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to randomization and agree to use effective contraception, as defined in Section 5.7.2. 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: For UK subjects, abstinence is acceptable if this is the established and preferred contraception for the subject.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 429
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 171

Exclusion criteria:
1. 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.
2. Has had monoclonal antibody (mAb) for direct anti-neoplastic treatment within 4 weeks of randomization.
3. Has had chemotherapy, targeted small molecule therapy, or radiation therapy within at least 2 weeks of randomization.
4. Has not recovered from adverse events (ie, downgraded to = Grade 1 or to baseline) 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.
5. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
Note: Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days of randomization.
7. 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.
8. Has known active brain metastases and/or carcinomatous meningitis. Note: Known brain metastases are considered active, if any of the following criteria is applicable:
a. 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.
b. Neurological symptoms attributed to brain metastases have not returned to baseline.
c. Steroids were used for brain metastases within 28 days of randomization
9. Has active/history of pneumonitis requiring treatment with steroids or active/history of interstitial lung disease.
10. Has an active infection requiring systemic therapy.
11. 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.
12. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
13. 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.
14. 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 (eg CTLA-4, OX-40, CD137) or has previously participated in Merck MK-3475 clinical trials.
15. Has a known history of Hum

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

Health Condition(s) or Problem(s) studied

Metastatic Triple Negative Breast Cancer
MedDRA version: 20.0 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-

Trade Name: Capecitabine cell pharm
Product Name: Capecitabine cell pharm
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Capecitabine cell pharm
Product Name: Capecitabine cell pharm
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Other descriptive name: CAPECITABINE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Trade Name: Halaven
Product Name: Halaven
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ERIBULIN
CAS Number: 253128-41-5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.44-

Trade Name: Gemcitabine
Product Name: Gemcitabine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Gemcitabine Hydrochloride
CAS Number: 95058-81-4
Other descriptive name: GEMCITABINE HYDROCHLORIDE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1000-

Trade Name: Vinorelbine
Product Name: Vinorelbine
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: VINORELBINE
CAS Number: 71486-22-1
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Capecitabine
Ph

Primary Outcome(s)

Secondary Objective: (1) Objective: To compare progression-free survival (PFS) based on RECIST 1.1 as assessed by blinded central imaging vendor in all subjects.
(2) To compare overall response rate (ORR) per RECIST 1.1 by blinded central imaging vendor in all subjects.
(3) To evaluate PFS and ORR based on RECIST 1.1 as assessed by blinded central imaging vendor in subjects with PD-L1 positive tumors (CPS =10 and CPS =1).
(4) To evaluate 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 (CPS =10 and CPS =1) and in all subjects.
(5) To determine the safety and tolerability of pembrolizumab.

Primary end point(s): 1. Overall survival (OS) in subjects with CPS =10
2. OS in subjects with CPS =1
3. OS in all subjects

Main Objective: PD-L1 Positive Populations: subjects with PD-L1 positive expression defined by =10
Combined Positive Score (CPS) and by =1 CPS; henceforth abbreviated as CPS =10 and
CPS =1 respectively.
(1) To compare OS in subjects with PD-L1 positive tumors (CPS =10).
(2) To compare OS in subjects with PD-L1 positive tumors (CPS =1).
(3) To compare OS in all subjects.

Timepoint(s) of evaluation of this end point: •Interim Analysis
Timing: approximately 14 months after enrollment is completed. It is estimated that ~ 130, 284 and 445 OS events will be accrued in subjects with CPS =10, CPS =1 and all subjects.
Purpose: interim efficacy analysis for OS

•Final analysis
- Triggered by duration of follow-up and OS events in subjects with CPS =1: ~ 24 months after enrollment is completed or 334 OS events accrue in subjects with CPS =1, whichever occurs later. ~ 154, 334 and 520 OS events will be accrued in subjects with CPS =10, CPS =1 and all subjects.
- If OS events in subjects with CPS =1 accrue slower than expected and fewer than 334 events are observed 26 months after enrolment is completed, then the Sponsor will conduct the final analysis at that time
Purpose: final efficacy analysis for OS

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Analysis of the secondary endpoints will be provided at IA-efficacy

Secondary end point(s): - PFS based on RECIST 1.1 by blinded central imaging vendor in all subjects
- ORR based on RECIST 1.1 by blinded central imaging vendor in all subjects
- PFS based on RECIST 1.1 by blinded central imaging vendor in subjects with CPS =10 and subjects with CPS =1
-ORR based on RECIST 1.1 by blinded central imaging vendor in subjects with CPS =10 and subjects with CPS =1
- DCR based on RECIST 1.1 by blinded central imaging vendor in subjects with CPS =10, subjects with CPS =1 and all subjects
- DOR based on RECIST 1.1 by blinded central imaging vendor in subjects with CPS =10, subjects with CPS =1 and all subjects

Secondary ID(s)

2015-001020-27-DE

MK-3475-119

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 29/02/2016
Contact: