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Trial record 58 of 175 for:    pertuzumab

A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1) (Keyriched-1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03988036
Recruitment Status : Not yet recruiting
First Posted : June 17, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
Amgen
NanoString Technologies, Inc.
Information provided by (Responsible Party):
West German Study Group

Tracking Information
First Submitted Date  ICMJE March 7, 2019
First Posted Date  ICMJE June 17, 2019
Last Update Posted Date October 1, 2019
Estimated Study Start Date  ICMJE November 2019
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
Evaluation of the pCR rate of the combination therapy consisting of pembrolizumab in combination with the dual anti-HER2 blockade trastuzumab biosimilar ABP 980 and pertuzumab in patients with HER2-enriched early breast cancer assessed by PAM50 testing [ Time Frame: After neoadjuvant treatment (planned duration of treatment is 12 weeks) ]
pCR defined as no invasive tumor in breast and lymph nodes (ypT0/is, ypN0) at surgery after study treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03988036 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 14, 2019)
  • Number and percentage of fatal adverse events as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.
  • Number and percentage of serious treatment-emergent adverse events as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.
  • Number and percentage of treatment-related adverse events as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.
  • Number and percentage of treatment-emergent adverse events of interest as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.
  • Number and percentage of adverse events leading to investigational product discontinuation [ Time Frame: 9 months for individual participants ]
    AEs classified by System Organ Class (SOC) and Preferred Terms (PT), descriptive analysis by number of observations and their percentage.
  • Number and percentage of severity of adverse events as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    Descriptive analysis by number of observations and their percentage.
  • Number and percentage of causality of adverse events as assessed by investigator and sponsor [ Time Frame: 9 months for individual participants ]
    Descriptive analysis by number of observations and their percentage.
  • Number and percentage of outcome of adverse events as per investigator assessment [ Time Frame: 9 months for individual participants ]
    Descriptive analysis by number of observations and their percentage.
  • Number and percentage of seriousness of adverse events as assessed by CTCAE 5.0 [ Time Frame: 9 months for individual participants ]
    Descriptive analysis by number of observations and their percentage.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype (Keyriched-1)
Official Title  ICMJE A Prospective, Multicenter, Open Label, Neoadjuvant Phase II Single Arm Study With Pembrolizumab in Combination With Dual Anti-HER2 Blockade With Trastuzumab and Pertuzumab in Early Breast Cancer Patients With Molecular HER2-enriched Intrinsic Subtype
Brief Summary Keyriched-1 is a multicenter, interventional, prospective, single arm, open label, neoadjuvant phase II trial evaluating the pathological complete response (pCR) rate induced by pembrolizumab in combination with the dual anti-HER2 blockade consisting of trastuzumab biosimilar ABP 980 and pertuzumab in early breast cancer patients with molecular HER2-enriched intrinsic subtype tested by PAM50.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Pembrolizumab
    Intravenous infusion; 200 mg; every 3 weeks
  • Drug: Trastuzumab Biosimilar ABP 980
    Intravenous infusion; 8 mg/kg loading dose, thereafter 6 mg/kg; every 3 weeks
  • Drug: Pertuzumab
    Intravenous infusion; 840 mg/kg loading dose, thereafter 420 mg/kg; every 3 weeks
Study Arms  ICMJE Experimental: HER2-enriched
Interventions:
  • Drug: Pembrolizumab
  • Drug: Trastuzumab Biosimilar ABP 980
  • Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: June 14, 2019)
46
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 2021
Estimated Primary Completion Date July 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.
  • Have previously untreated, non-metastatic (M0) HER2-enriched breast cancer defined as the following combined primary tumor (T) and regional lymph node (N) staging per American Joint Committee on Cancer (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

  • Patients with HER2-enriched, estrogen and/ or progesterone receptor positive or negative breast cancer defined by American Society of Clinical Oncology (ASCO) / College of American Pathologists (CAP) guidelines can be included.
  • Availability of tumor imaging performed within three months prior to start of screening phase: breast ultrasound and computed tomography (CT) thorax/abdomen or chest X-ray/liver ultrasound, bone scan, mammography or breast magnetic resonance imaging (MRI) (according to local standard).
  • 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.

  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and if at least one of the following conditions applies:

    1. Not a woman of childbearing potential (WOCBP) as defined in Appendix 3 OR
    2. 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.

  • 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.

During the screening phase, the following criteria must be confirmed for the participant to remain in the study for treatment allocation. (If these criteria are not met, the patient becomes a screening failure).

  • Confirmation of a HER2neu [immunohistochemistry (IHC) 2+ status and amplification (e.g. fluorescence in situ hybridization (FISH))] or [IHC 3+ status] tumor identification by local pathology.
  • Confirmation of HER2-enriched status by PAM50 testing.
  • Confirmed HR+ or HR- status.
  • The female participant 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.

  • Have a 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.
  • Have a normal electrocardiogram (ECG) performed at screening or performed in clinical routine within 6 weeks prior to first treatment allocation.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 10 days prior to the date of treatment initiation.
  • Have adequate organ function as defined in the following table. Specimens must be collected within 10 days prior to the start of study treatment.

Exclusion Criteria:

  • 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.
  • 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 acverse events 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.

  • 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.
  • 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.

  • 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.
  • 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.
  • Has a known hypersensitivity to the components of the study therapy, its analogs, murine proteins or any of the excipients.
  • 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.
  • Has a significant cardiovascular disease, such as: LVEF < 55%, history of myocardial infarction, acute coronary syndrome or coronary angioplasty/stenting/bypass grafting within the past 6 months.
  • Congestive heart failure (CHF) New York Heart Association (NYHA) Class I-IV or history of CHF NYHA class III or IV.
  • Severe and relevant co-morbidity that would interact with the application of cytotoxic agents or the participation in the study including but not confined to: unstable arrhythmias requiring treatment i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia (ventricular tachycardia) or higher-grade AV-block, angina pectoris within the last 6 months requiring anti-anginal medication, clinically significant valvular heart disease, evidence of myocardial infarction on ECG, poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100 mm Hg).
  • 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).
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a known history of Human Immunodeficiency Virus (HIV).
  • Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection.
  • Has a known history of active TB (Bacillus Tuberculosis).
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive children or planning to breast-feed within the projected duration of the study, starting with the screening visit through 7 months after end of treatment.
  • Male patients with breast cancer.
  • History of breast cancer.
  • Reasons indicating risk of poor compliance.
  • Thrombocytopenia > common terminology criteria for adverse events (CTCAE) grade 1, increases in ALT/AST > CTCAE grade 1, hypokalaemia > CTCAE grade 1, neutropenia > CTCAE grade 1, anaemia > CTCAE grade 1.
  • Non-operable breast cancer including inflammatory breast cancer.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sherko Kuemmel, Professor +4920117433001 s.kuemmel@kem-med.com
Contact: Anja Lomnitz +4921615662325 anja.lomnitz@wsg-online.com
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03988036
Other Study ID Numbers  ICMJE WSG-AM09
2018-003996-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party West German Study Group
Study Sponsor  ICMJE West German Study Group
Collaborators  ICMJE
  • Merck Sharp & Dohme Corp.
  • Amgen
  • NanoString Technologies, Inc.
Investigators  ICMJE
Principal Investigator: s.kuemmel@kem-med.com Kuemmel, Professor Clinics Essen-Mitte, Breast Center
PRS Account West German Study Group
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP