Group 3: Triple negatice breast cancer.
Triple negative breast cancer.
Triple negative breast cancer (TNBC)
Participants must have histologically or cytologically confirmed disease from melanoma, triple negative breast cancer, head and neck cancer, lung cancer, bladder cancer, renal cell cancer
Triple Negative Breast Cancer (TNBC) (D
RANDOMIZED PHASE II CLINICAL TRIAL: Women diagnosed with pathologically confirmed triple negative invasive breast cancer, metastatic (locally confirmed immunophenotype negative for all three receptors ER, PR, HER2)
Histologically documented HER2-positive and HER2-negative (cohort E only) breast cancer
Histologically confirmed triple negative breast cancer that are refractory, intolerant, or ineligible to receive approved standard therapies
Have a diagnosis of metastatic triple negative breast cancer (TNBC) • Up to 1-2 prior lines of chemotherapy
Histopathological diagnosis of metastatic or inoperable locally advanced triple negative breast cancer (TNBC) that meets the following criteria:\r\n* Triple negative is generally defined as estrogen receptor (ER) < 1%, progesterone receptor (PR) < 1%, and HER2 negative according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines by local testing according to institutional standards\r\n** Note: for tumors with equivocal interpretation of receptor status (e.g., ER/PR >= 1% “weak” or “faint” staining), the principal investigator will have final determination of triple-negative status; for tumors with discrepant receptor results between 2 or more biopsies (including metastatic and/or early stage biopsies), the principal investigator will have final determination of triple negative status, but in general the most recent biopsy can be used for eligibility purposes; if receptor testing is not available on a metastatic biopsy, the primary tumor test result is acceptable\r\n* Metastatic or inoperable locally advanced disease is defined as either: histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease without a documented metastatic biopsy, provided the patient has a prior diagnosis of TNBC that otherwise meets the eligibility criteria\r\n* Ductal, lobular, mixed, or metaplastic histology
Presence of measurable disease as defined by RECIST version 1.1 Cohort 3: Patient Population: Relapsed/Refractory Triple Negative Breast Cancer
advanced triple negative breast cancer,
Any prior chemotherapy, hormonal, or targeted therapy, for inoperable locally advanced or metastatic triple-negative breast cancer (mTNBC)
Patients must be diagnosed with locally advanced (T2 and higher with or without lymph node involvement), and/or inflammatory triple negative breast cancer
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients must have received at least one line of prior chemotherapy in the metastatic setting
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients must have measurable disease, per RECIST 1.1
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: ECOG performance status 0 or 1
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: AST and ALT levels =< 3 X ULN
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Absolute neutrophil (ANC) >= 1,500/mm^3 (>= 1.5 X 10^6/L)
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Platelet count >= 75,000/mm^3 (>= 75 X 10^6/L)
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients who have undergone radiotherapy within 4 weeks of first dose of study treatment
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients with a history of another invasive malignancy within the last 3 years
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: HIV-positive patients on combination antiretroviral therapy are ineligible
COHORT 2: TRIPLE NEGATIVE BREAST CANCER: Patients who have known active hepatitis B, or hepatitis C infections
Histologically confirmed triple negative breast cancer(TNBC) that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic
Triple Negative tumors: Must have exhausted other available therapies including prior treatment with a taxane and carboplatin. Patients with new or progressive breast cancer metastatic to brain will be eligible provided:
COHORT 1 (TRIPLE-NEGATIVE BREAST CANCER [TNBC])
Locally advanced and unresectable or metastatic TNBC or triple negative inflammatory breast cancer.
Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer
Subjects must have received no more than 2 prior therapies for metastatic triple-negative breast cancer
Metastatic or unresectable AR+ triple-negative breast cancer (TNBC); AR positivity assessed centrally and defined as immunohistochemical (IHC) staining of >0% of tumor nuclei.
Diagnosis of triple-negative or ER-negative breast cancer
HER2/neu positive or estrogen and progesterone receptor negative breast cancer; patients with triple negative breast cancer are also excluded
At least 10 HER2-negative breast cancer patients will be enrolled in this cohort
Women already undergoing neoadjuvant chemotherapy to treat their primary triple negative breast cancer
Histological documentation of advanced solid tumor, other than triple-negative breast cancer (TNBC).
Triple-negative tumours, i.e. tumour cells are negative for
Histologically confirmed invasive triple negative Breast Cancer
For the dose expansion cohort, patients with triple-negative breast cancer may not be BRCA1/2 germline mutation carriers
Pre- or post-menopausal women with stage I and II breast cancer, triple negative tumors (upper limit of positivity < 10% for estrogen receptors, < 20% for progesterone receptors)
Pathologically confirmed as triple negative, source documented, defined as both of the following:
Triple Negative Breast Cancer
Cohort 1: Participants must have triple negative breast cancer.
Patients enrolled on the expansion portion of the study will consist of two cohorts: those patients who are triple-negative, BRCA-mutant positive and those patients who have triple-negative, non-BRCA mutated breast cancer
triple-negative adenocarcinoma of the breast
Triple-negative breast cancer (TNBC) defined as histologically confirmed diagnosis of breast cancer and must have received at least 1 chemotherapy-containing regimen for advanced disease (recurrent or metastatic). Tumour must be triple-negative, defined as minimal or no expression of estrogen and progesterone receptors [<10% of cells positive by immunohistochemistry (IHC)], and minimal or no expression of HER2 (IHC staining 0 or 1+ or FISH-).
Metastatic triple negative breast cancer (TNBC)
Histologically- or cytologically-confirmed ovarian cancer, colorectal cancer, non-triple negative breast cancer, renal cell carcinoma and cervical cancer, with at least one lesion measurable by irRC not previously irradiated.
Phase l: Melanoma, RCC, triple negative breast cancer, bladder cancer, head and neck cancer or non-small cell lung cancer.
For maximum tolerated dose (MTD) Dose Expansion: Subjects with advanced, histologically or cytologically confirmed triple-negative breast cancer who had undergone within 4 lines of systemic anti-cancer treatment and not eligible for standard therapy anymore.
Cohort 1: Has triple negative breast cancer, is considered for cohort 1 participation, and received prior anthracycline therapy
For the expansion cohort: women with histologically or cytologically confirmed TNBC (triple negative breast cancer)
Patient has a confirmed diagnosis of a select solid tumor (except breast cancer (however, triple negative will be included), liposarcoma, CRPC, melanoma and teratoma) or hematological malignancy (except mantle cell lymphoma).
Previously treated metastatic triple negative breast cancer that expresses Notch3 with at least one measurable lesion
Part 2 includes advanced triple negative breast cancer patients.
Expansion phase only: Subjects with advanced, histologically or cytologically confirmed gastric cancer, triple negative breast cancer (TNBC), or diffuse large B-cell lymphoma (DLBCL), who were refractory to or had exhausted all available therapies. Subjects had to have evaluable or measurable disease (as per RECIST 1.1 or Cheson 2007 criteria).
Subjects with non-small cell lung cancer and triple-negative breast cancer are preferred
For the dose expansion cohort, patients with triple-negative breast cancer may not be breast cancer 1/2 (BRCA1/2) germline mutation carriers
Triple negative breast cancer
Participants must have histologically confirmed diagnosis of locally advanced and/or metastatic triple negative breast cancer, ovarian cancer, bladder cancer, gastric cancer, or soft tissue sarcoma, with exceptions defined in the exclusion criteria
Patients with tumors of two different subtypes will be eligible provided that the triple negative tumor otherwise meets eligibility requirements, and the non-triple negative tumor is < 1.0 cm in size
Criteria1, Participant provided informed consent prior to any study-specific activities/procedures -Criteria 2, Confirmation of triple negative breast cancer or colorectal cancer with liver metastases by laboratory testing