A Phase II Study of Pembrolizumab in Subjects with Triple-Negative Breast Cancer
- Conditions
- Triple-Negative Breast CancerMedDRA version: 20.0Level: PTClassification code 10075566Term: Triple negative breast cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2015-000294-13-DE
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 285
For Cohorts A and C (2L+ monotherapy), potential subjects must:
1. Have received at least one systemic treatment for metastatic breast cancer and have documented disease progression on or after the most recent therapy. Subjects must have been previously treated with an anthracycline and a taxane in the (neo)adjuvant or metastatic setting.
Note for Cohort A: In the event that the interim analysis shows that pembrolizumab monotherapy is futile in subjects with PD-L1 (-) mTNBC, subsequent enrollment to Cohort A may be limited to subjects with PD-L1 (+) tumors. If this is the case, sites will be notified via a Protocol Clarification Letter.
For Cohort B (1L monotherapy), potential subjects must:
2. Have not received prior systemic anti-cancer therapy for mTNBC, and
3. Have PD-L1 (+) mTNBC.
For the purposes of this study, neoadjuvant and/or adjuvant chemotherapy regimens do not count as a prior line of therapy.
For Cohort C (2L+ monotherapy), potential subjects must:
4. Have PD-L1 strong (+) mTNBC, i.e. subject’s tumor must meet or exceed the PD-L1 cut point for high positivity.
For all cohorts, potential subjects must:
5. Be willing and able to provide written informed consent/assent for the trial. The subject may also provide consent/assent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
6. Be = 18 years of age on day of signing informed consent.
7. Be a female or male subject with mTNBC. Central determination of triple-negative breast cancer status is required for enrollment.
8. Have provided tumor tissue for PD-L1 biomarker analysis from a newly obtained core or excisional biopsy of a not-previously-irradiated metastatic tumor lesion (mandatory). Adequacy of the biopsy specimen for PD-L1 biomarker analysis must be confirmed by the central analysis laboratory. Repeat samples may be required if adequate tissue is not provided.
a. Note: Subjects for whom tumor biopsies cannot be newly obtained (e.g. inaccessible tumor or subject safety concern) may submit an archived metastatic tumor specimen only upon agreement from the sponsor.
b. Note: If emerging data demonstrates that there is no difference in the clinical utility of PD-L1 assessment in newly obtained samples relative to archived ones, then archived samples may be acceptable without Sponsor agreement. If this is the case, sites will be notified via an Administrative Memo.
c. Note: For subjects with mTNBC at the time of inital breast cancer diagnosis, who did not have breast surgery and/or breast Radiation therapy, a newly obtained core or excisional biopsy from the existing breast Tumor mass may be obtained for eligibility determination.
9. Have measurable metastatic disease based on RECIST 1.1 as determined by the central imaging vendor. Tumor lesions situated in a previously irradiated area are considered measurable, if radiographic progression has been demonstrated in such lesions.
a. Note: The same imaging modality, acquisition and technical parameters should be used throughout the study for tumor imaging.
10. Have a performance status of 0 or 1 on the ECOG Performance Scale. Assessment should be performed within 10 days of treatment initiation.
11. Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days aft
1. Is currently participating and receiving study therapy, 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 treatment.
Note: Subjects who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks since the last dose of the previous investigational agent or device.
2. 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 (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3. 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.
4. Has had a prior anti-cancer monoclonal antibody (mAb) for direct anti-neoplastic treatment 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.
5. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within at least 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.
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 intervention prior to starting therapy.
6. 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, or in situ cervical cancer.
7. 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.
8. Has history of (non-infectious) pneumonitis that required steroids or current pneumonitis or history of interstitial lung disease.
9. Has an active infection requiring systemic therapy.
10. 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.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. 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.
13. 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 participated in Merck MK-3475 trials.
14. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
15. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatit
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method