A Safety Study of SGN-LIV1A in Breast Cancer Patients

Inclusion Criteria:

* Pathologically confirmed diagnosis of breast cancer with radiographic evidence of incurable, unresectable, locally advanced or metastatic disease (LA/MBC)
* One of the following:

  * Part A: Triple-negative disease (ER/PR/HER2-negative) and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or ER-positive and/or PR-positive/HER2-negative disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting and are no longer a candidate for hormonal therapy (not enrolling new patients);
  * Part B: Combination Arm: HER2-positive disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting (not enrolling new patients);
  * Part C: Triple-negative disease and received 2-4 prior non-hormonally-directed therapies in the MBC setting (not enrolling new patients);
  * Part D and Part E (dose-expansion cohort): Triple-negative disease and received 1 prior non-hormonally-directed or cytotoxic therapy in the MBC setting; or
  * Part E: HR+(ER-positive and/or PR-positive)/HER2-negative disease who are chemotherapy-eligible and not considered a candidate for further hormonal therapy. Must have received no more than 1 prior non-hormonally-directed or cytotoxic therapy in the LA/MBC setting.
* Part F: All of the following:

  * Triple negative breast cancer
  * No prior cytotoxic chemotherapy for unresectable locally advanced or metastatic stage disease
  * Tumor tissue PD-L1 expression CPS \<10 expression
* Parts A, B, C, and D: Newly obtained or archived tumor tissue biopsy, must be collected for central pathology determination of LIV-1 expression
* Parts E and F: Archival or fresh baseline tumor sample is required.
* Measurable disease
* Eastern Cooperative Oncology Group performance status 0 or 1
* Combination Arm: adequate heart function

Exclusion Criteria:

* Pre-existing neuropathy Grade 2 or higher
* Parts A, B, C, and D: Cerebral/meningeal disease that is related to the underlying malignancy and has not been definitively treated. Parts E and F: Known or suspected cerebral/meningeal metastasis that has not been definitively treated.
* Prior treatment with LV or prior treatment with an MMAE-containing therapy
* Combination Arm: hypersensitivity to trastuzumab