Clinical Trial 18862

Cancer Type: Breast
Interventions:Herceptin (Trastuzumab); SGN-LIV1A; Trastuzumab; rhuMAb HER2 (Trastuzumab)

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Heather Han

Overview

Study Title

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

Summary

This study is being done to find out what side effects (unwanted effects) are caused in participants with breast cancer who are given SGN-LIV1A (single therapy). This study will also look at other effects of SGN-LIV1A, including its effect on this type of cancer. This study is also being done to find out what side effects (unwanted effects) are caused in participants with HER2-positive breast cancer who are given SGN-LIV1A in combination with trastuzumab (combination therapy).

Objective

Primary Objectives: - To evaluate the safety and tolerability of SGN-LIV1A in patients with LIV-1-positive, incurable, unresectable, LA/MBC. - To identify the maximum tolerated dose (MTD) of SGN-LIV1A, if one exists among doses tested. - To evaluate the safety and tolerability of treatment with SGN-LIV1A given in combination with trastuzumab to patients with HER2-positive- and LIV-1-positive LA/MBC (Part B only). Secondary Objectives: - To assess the pharmacokinetics (PK) of SGN-LIV1A. - To assess the immunogenicity of SGN-LIV1A. - To assess the antitumor activity of SGN-LIV1A. Additional Objectives: - To assess exploratory biomarkers of SGN-LIV1A-mediated pharmacodynamic effects and to evaluate LIV-1 expression in tumor tissue. - To evaluate the LIV-1 expression-response relationship following treatment with SGN-LIV1A.

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: a) Triple-negative disease (ER/PR/HER2-negative) and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or b) ER- 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; or c) Combination Arm: HER2-positive disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting.
  • Positive for LIV-1 expression by central pathology review on archival or newly obtained tumor tissue biopsy
  • 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
  • Malignant CNS disease that has not been definitively treated
  • P-gp inducers/inhibitors or strong CYP3A inducers/inhibitors within 2 weeks before first dose
  • Combination Arm: hypersensitivity to trastuzumab