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

• Register: EUCTR
• Last refreshed on: 8 October 2021
• Main ID: EUCTR2015-001020-27-ES
• Date of registration: 15/10/2015
• 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 mTNBC
• Date of first enrolment: 02/12/2015
• Target sample size: 600
• Recruitment status: Not Recruiting
• 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, Italy, 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: Investigación Clínica
• Affiliation: Merck Sharp & Dohme de España S.A.

• Name: Investigación Clínica
• Affiliation: Merck Sharp & Dohme de España S.A.

Key inclusion & exclusion criteria

Inclusion criteria:
1.Have received either one or two prior systemic treatments for metastatic breast cancer and have documented disease progression on the most recent therapy.
2.Have been previously treated with an anthracycline and/or taxane in the (neo)adjuvant or metastatic setting.
3.Have centrally confirmed mTNBC (determined by a newly obtained core or excisional biopsy from a metastatic, not previously irradiated, tumor lesion).
4.Have measurable disease based on RECIST 1.1 as assessed by investigator and local radiology review.
5.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.
6.Have an ECOG performance status of 0 or 1 assessed within 10 days of treatment initiation.
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 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 in a study of an investigational agent/device and has received/is receiving the investigational agent/device within 4 weeks of randomization.
Note: Subjects who have 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 (i.e., < or = to Grade 1 or at baseline) from adverse events due to a previously administered therapy.
Note: Subjects with < or = to 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 (i.e. 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 radiographically detectable (even if asymptomatic and/or previously treated) central nervous system (CNS) metastases and/or carcinomatous meningitis. Brain imaging at screening is required.
9.Has history of pneumonitis requiring treatment with steroids or 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.
14.Has received prior therapy with an anti-PD-1, anti-PD-L1, 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.
15.Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16.Has a known history of 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


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

Health Condition(s) or Problem(s) studied

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

Metastatic Triple Negative Breast Cancer

Intervention(s)

Trade Name: Keytruda
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 MESILATE
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-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 2 IA and results revision by an eDMC.IA 1:after (1) ~400 subjects are enrolled, and (2) ~280 subjects have more than 3 months of follow-up, and (3) ~70 PFS events have been observed among subjects with PD-L1 negative tumors.IA 2:after enrollment is completed and, in subjects with PD-L1 positive tumors, at least 286 subjects have been followed for at least 3 months and approximately 185 PFS events or more have been observed; the analysis may be delayed for up to 2 months, if less than ~100 OS events have been observed in subjects with PD-L1 positive tumors.

Main Objective: 1st Objective: 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. 2nd Objective: To compare PFS based on RECIST 1.1 as assessed by blinded central imaging vendor in all subjects. 3rd Objective: To compare overall survival (OS) in subjects with PD-L1 positive tumors. 4th Objective: To compare OS in all subjects.

Secondary Objective: 1st Objective: To estimate 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. 2nd Objective: To determine the safety and tolerability of pembrolizumab.

Primary end point(s): Progression-free Survival (PFS) based on RECIST 1.1 as assessed by blinded central imaging vendor in subjects with PD-L1 positive tumors
2. PFS based on RECIST 1.1 as assessed by blinded central imaging vendor in all subjects
3. Overall Survival (OS) in subjects with PD-L1 positive tumors
4. OS in all subjects

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: When subjects are evaluable through response, progression or 12-week scan, whichever comes first.

Secondary end point(s): ORR/DCR
Based on RECIST 1.1 by blinded central imaging vendor in subjects with PD-L1 positive tumors and inall subjects Stratified M & N method?
ITT /DOR
Based on RECIST 1.1 by blinded central imaging vendor in subjects with PD-L1 positive tumors and in all subjects Summary statistics using Kaplan-Meier method

All responders in ITT

Secondary ID(s)

3475-119

2015-001020-27-DE

Source(s) of Monetary Support

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

Ethics review

Status: Approved
Approval date: 06/11/2015
Contact: