A Safety Study of SGN-LIV1A in Breast Cancer Patients

A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of SGN-LIV1A in Patients With Metastatic Breast Cancer

This study will examine the safety and tolerability of ladiratuzumab vedotin (LV) in patients with metastatic breast cancer. LV will be given alone or in combination with trastuzumab.

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