A Safety Study of SGN-LIV1A in Breast Cancer Patients

Seagen

Status and phase: Completed; Phase 1

Conditions: HER2 Positive Breast Neoplasms; Hormone Receptor Positive Breast Neoplasms; Triple Negative Breast Neoplasms; HER2 Mutations Breast Neoplasms

Treatments: Drug: ladiratuzumab vedotin; Drug: Trastuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT01969643

SGNLVA-001

Details and patient eligibility

About

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.

Enrollment: 290 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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290 participants in 3 patient groups

LV Dose Escalation

Experimental group

Treatment:

Drug: ladiratuzumab vedotin

LV + Trastuzumab

Experimental group

Treatment:

Drug: Trastuzumab

Drug: ladiratuzumab vedotin

LV Monotherapy

Experimental group

Description:

LV will be given at the recommended dose (at or below the monotherapy MTD determined in the LV dose escalation arm).

Treatment:

Drug: ladiratuzumab vedotin