eoadjuvant therapy with Pembrolizumab in combination with anti-HER2-blockade with trastuzumab and pertuzumab in early breast cancer patients with HER2+ and hormonal receptor positive or negative early breast cancer.
- Conditions
- HER 2+/HR+ and HR- early breast cancerMedDRA version: 21.1Level: LLTClassification code 10006188Term: Breast cancer female NOSSystem Organ Class: 100000004864MedDRA version: 20.0Level: LLTClassification code 10006192Term: Breast cancer NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003996-37-DE
- Lead Sponsor
- Westdeutsche Studiengruppe GmbH (WSG)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 46
Patients eligible for inclusion in this study have to meet all of the following criteria:
1.Female participants, who are at least 18 years of age on the day of signing informed consent with newly histologically locally confirmed diagnosis of HER2neu 2+ or 3+ breast cancer.
2.Previously untreated, non-metastatic (M0) HER2-enriched breast cancer 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, N0-N2; T2, N0-N2; T3, N0-N2.
3.Patients with HER2-enriched, estrogen and/ or progesterone receptor positive or negative breast cancer defined by ASCO/ CAP guidelines can.
4.Availability of tumor imaging performed within three months prior to start of screening phase: Breast Ultrasound and CT Thorax/Abdomen or Chest X-ray/liver Ultrasound, Bone Scan, Mammography or Breast MRI (according to local standard).
5.Ability to provide archived tumor tissue sample or at least two newly obtained separate tumor cores from the primary tumor or excisional biopsy of a tumor lesion not previously irradiated at screening to the central laboratory. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred over slides. Newly obtained biopsies are preferred over archived tissue.
Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut.
6.A female participant is eligible to participate if she is not pregnant, not breastfeeding, and if at least one of the following conditions applies:
a.) Not a woman of childbearing potential (WOCBP) as defined in Appendix 3
OR
b.) A WOCBP who agrees to follow the contraceptive guidance in Appendix 3 during the treatment period and for at least 7 months after the last dose of study treatment
NOTE: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the participant.
7.The participant provides written informed consent for the trial. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.
8.Confirmed HER2neu [IHC 2+ status and amplification (e.g. FISH)] or [IHC 3+ status] tumor identification by local pathology.
9.Confirmed HER2-enriched status by PAM 50 testing.
10.Confirmed HR + or HR – status.
11.Female patients of childbearing potential must have a negative urine or serum pregnancy 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.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
12.Left ventricular ejection fraction (LVEF) of =55% or = institution lower limit of normal (LLN) as assessed by echocardiogram (ECHO) or multigated acquisition (MUGA) scan performed at screening or performed in clinical routine within 6 weeks prior to first treatment allocation.
13.Normal ECG performed at screening or performed in clinical routine within 6 weeks prior to first treatment allocation.
14.Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluatio
Participants are excluded from the study if any of the following criteria apply:
1.Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T cell receptor (eg, CTLA-4, OX 40, CD137) or has participated in MK-3475 clinical trials.
2.Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of study medication.
Note: Participants must have recovered from all AEs due to previous therapies to =Grade 1 or baseline. Participants with =Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
3.Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
4.Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent. Participant should be excluded if she received an investigational agent with anti-cancer or anti-proliferative intent within the last 12 months.
5.Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
6.Prior malignancy with a disease-free survival of = 5 years before signing informed consent. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
7.Has a known hypersensitivity to the components of the study therapy, its analogs, murine proteins or any of the excipients.
8.Has 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.
9.Has a significant cardiovascular disease.
10.Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study.
11.Inadequate organ function including but not confined to:
•hepatic impairment (Child Pugh Class C),
•pulmonary disease (severe dyspnea at rest due to complications of advanced malignancy or requiring oxygen therapy).
12.Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
13.Has an active infection requiring systemic therapy.
14.14.Patient has a known history of human immu
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