A Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer
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Keep this study
Lead
Hoffmann-La Roche
Age
18–any
Sex
ALL
Healthy volunteers
Not accepted
You may be eligible if
Histologically or cytologically confirmed invasive metastatic breast cancer (MBC) or locally advanced breast cancer (LABC) that is incurable, unresectable, and previously treated with multimodality therapy
Measurable disease that is evaluable per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Willing to provide tumor biopsy sample at the time of screening
Local histological or cytological confirmation of estrogen receptor (ER) and/or progesterone receptor status as defined by using immunohistochemistry (IHC) per American Society of Clinical Oncology/College of American Pathologists criteria
Percentage of ER and/or progesterone receptor positivity, if available
Willing to provide blood samples at the time of screening, on-study, and at progression for exploratory research on biomarkers
HER2-positive BC as defined by an IHC score of 3+ or gene amplified by in situ hybridization (ISH) as defined by a ratio of \>/= 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies
Adequate hematologic and end-organ function
Screening left ventricular ejection fraction (LVEF) \>/= 50% on echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan
Negative HIV test, hepatitis B surface antigen (HBsAg), total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating sperm during the treatment period and for at least 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine
Trastuzumab emtansine experienced cohort: Disease progression during or after trastuzumab emtasine in the advanced/metastatic setting or disease recurrence in the neoadjuvant/adjuvant setting; At least 50% of participants in the expansion cohort must have a tumor that is Bcl-2 high (defined as \>50% of tumor cells stained with an intensity of immunohistochemistry (IHC) 2+ or 3+)
Trastuzumab deruxtacan (DS-8201a) experienced cohort: Disease progression during or after trastuzumab deruxtecan in the advanced/metastatic setting; Prior trastuzumab emtansine in any setting is allowed; At least 50% of participants in the expansion cohort must have a tumor that is Bcl-2 high
You may not be if
Receipt of any anticancer drug/biologic or investigational treatment 21 days prior to Cycle 1, Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1, Day 1
Radiation therapy within 2 weeks prior to Cycle 1, Day 1
History of exposure to the following cumulative doses of anthracyclines as specified: Doxorubicin \>500 mg/m2; Liposomal doxorubicin \>500 mg/m2; Epirubucin \>720 mg/m2; Mitoxantrone \>120 mg/m2; Idarubicin \>90 mg/m2. If another anthracycline or more than one anthracycline has been used, then the cumulative dose must not exceed the equivalent of 500 mg/m2 doxorubicin.
History of other malignancy within the previous 5 years
Cardiopulmonary dysfunction
Current severe, uncontrolled systemic disease
Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1, Day 1
Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis, or active infection with HBV or HCV)
Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
Known HIV infection or human T-cell leukemia virus 1 infection
Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \> 2 weeks prior to randomization
Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
Current Grade \>/= 3 peripheral neuropathy
History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies, excipients of any drugs formulated in polysorbate 80 or 20 or fusion proteins
Prior allogeneic stem cell or solid organ transplantation
Pregnant or breastfeeding, or intending to become pregnant during the study or within 30 days after the last dose of venetoclax or 7 months after the last dose of trastuzumab emtansine after the final dose of study treatment, whichever is later
Consumption of grapefruit, grapefruit products, Seville oranges, or starfruit within 3 days before anticipated first dose of study drug until the last dose of study drug
Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study
Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment
Malabsorption syndrome or other condition that would interfere with enteral absorption
History of active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis) requiring specific medication in the 12 months prior to randomization, or active and uncontrolled bowel inflammation (e.g., diverticulitis) at time of randomization
Inability or unwillingness to swallow a large number of tablets
Known hypersensitivity to venetoclax or trastuzumab emtansine or to any of their excipients
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
Other medical or psychiatric conditions that, in the opinion of the investigator, may interfere with the patient's participation in the study
Blood transfusions if performed within 2 weeks prior to screening
Prior treatment with trastuzumab emtansine in any setting (neoadjuvant/adjuvant or advanced/metastatic setting)
Prior treatment with venetoclax in any setting
Prior treatment with anti-HER2 antibody drug conjugates (e.g. trastuzumab deruxtecan \[DS-8201a\]), margetuximab, pyrotinib, or tucatinib)
Clareo Health | A Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer
