Ensayos clínicos

Inclusion Criteria:

• Female or male patients with histologically confirmed HER2+ breast cancer who have completed chemotherapy in combination with P+H IV and are currently receiving or will be receiving maintenance P+H IV, PH FDC SC, or trastuzumab SC (regardless of remaining treatment cycles [e.g., only 1 cycle remaining]).
• HER2+ status must have been previously determined and is defined as 3+ by immunohistochemistry (IHC) and/or positive by HER2 amplification by in situ hybridization (ISH) with a ratio of ≥ 2 for the number of HER2 gene copies to the number of chromosome 17 copies.
• Patients are not restricted from restarting therapy at any time, per investigator’s discretion. However, upon re-initiation of chemotherapy patients will be discontinued from this study.
• Signed Informed Consent Form by patient or the patient’s legally-authorized representative.
• Age ≥ 18 years at time of signing Informed Consent Form.
• Ability to comply with the study protocol, in the investigator’s judgment.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
• Intact skin at planned site of subcutaneous (SC) injections (thigh).
• Baseline and most recent (within 3 months) LVEF ≥ 50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA).
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating eggs, as defined below:
  • Women must remain abstinent or use non-hormonal contraceptive methods with a failure rate of < 1% per year, or 2 effective non-hormonal contraceptive methods during the study treatment periods and for 7 months after the last dose of study treatment. Women must refrain from donating eggs during this same period;
  • A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a post-menopausal state (post-menopausal defined as ≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements;
  • Examples of non-hormonal contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization (with appropriate post-vasectomy documentation of the absence of sperm in the ejaculate) and copper intrauterine devices (IUDs);
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below:
  • With female partners of childbearing potential or pregnant female partners,men must remain abstinent or use a condom during the study treatment periods and for seven months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period;
  • The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of preventing drug exposure.

Exclusion Criteria:

• Current or prior history of active malignancy (other than current breast cancer) within the last 5 years. Appropriately treated non-melanoma skin cancer; in situ carcinomas, including cervix, colon, or skin; or Stage I uterine cancer within the last 5 years are allowed.
• Investigational treatment within 4 weeks of enrollment.
• Patients with any severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infections should not be enrolled in the trial (in the current situation, this also applies to patients with suspected or confirmed COVID-19 infection).
  • Patients with suspected or confirmed COVID-19 may be re-screened for eligibility following physician-prescribed COVID-19 treatment and/or quarantine and following a negative COVID-19 real-time reverse transcription polymerase chain reaction (rRT-PCR) test.
• Patients who may have had a recent episode of thromboembolism and are still trying to optimize the anticoagulation dose and/or have not normalized their INR.
• Serious cardiac illness or medical conditions including, but not confined to, the following:
  • History of NCI CTCAE v5.0 Grade ≥ 3 symptomatic congestive heart failure (CHF) or New York Heart Association (NYHA) Class ≥ II;
  • High-risk uncontrolled arrhythmias (i.e., atrial tachycardia with a heart rate ≥ 100/min at rest, significant ventricular arrhythmia [ventricular tachycardia], or higher-grade atrioventricular [AV]-block, such as second-degree AV-block Type 2 [Mobitz II] or third-degree AV-block);
  • Serious cardiac arrhythmia or severe conduction abnormality not controlled by adequate medication;
  • Angina pectoris requiring anti-angina medication;
  • Clinically significant valvular heart disease;
  • Evidence of transmural infarction on electrocardiogram (ECG);
  • Evidence of myocardial infarction within 12 months prior to enrollment;
  • Poorly controlled hypertension (e.g., systolic > 180 mm Hg or diastolic > 100mmHg).
• History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias, such as structural heart disease (e.g., severe left ventricular systolic dysfunction [LVSD], left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
• Inadequate bone marrow function, defined by any of:
  • Absolute neutrophil count (ANC) < 1.0 x 10^9/L;
  • Platelet count < 100 x 10^9/L;
  • Hemoglobin < 9 g/dL.
• Impaired liver function, defined by any of:
  • Serum (total) bilirubin > 1.25 x upper limit of normal (ULN). In case of Gilbert’s syndrome: a total bilirubin of 2 x ULN is permitted;
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as defined below:
  • Patients with early breast cancer: AST and ALT > 1.5 x ULN;
  • Patients with metastatic breast cancer: AST and ALT > 2.5 x ULN;
  • Patients with liver metastases: AST and ALT > 5 x ULN;
  • Albumin < 25g/L.
• Renal function with creatinine clearance < 50 mL/min using the Cockroft-Gault formula.
• Major surgical procedure unrelated to breast cancer within 28 days prior to study entry or anticipation of the need for major surgery during the course of study treatment.
• Current severe, uncontrolled systemic disease that may interfere with planned treatment (e.g., clinically significant cardiovascular, pulmonary, or metabolic disease; wound-healing disorders).
• Pregnant or breastfeeding, or intending to become pregnant during the study or within seven months after the last dose of study treatment.
• Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator’s judgment, precludes the patient’s safe participation in, and completion of, the study.
• Known active liver disease, for example, active viral hepatitis infection (i.e., hepatitis B or hepatitis C), autoimmune hepatic disorders, or sclerosing cholangitis.
• Concurrent, serious, uncontrolled infections, or known infection with human immunodeficiency virus (HIV).
  • Patients with known HIV who have adequate and stable CD4 counts on highly active antiretroviral therapy (HARRT) are allowed.
• Known hypersensitivity to any of the study drugs, excipients, and/or murine proteins or a history of severe allergic or immunological reactions; e.g., difficult to control asthma.
• Previously experienced severe injection related reactions with P + H IV, PH FDC SC and/or trastuzumab SC.
• Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent excluding inhaled steroids).

Eligibility last updated 2/17/22. Questions regarding updates should be directed to the study team contact.