Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer

Single Arm, Open Label Phase 1b/2 Study of SGN-LIV1A in Combination With Pembrolizumab for First-Line Treatment of Patients With Unresectable Locally-Advanced or Metastatic Triple-Negative Breast Cancer

This trial studies ladiratuzumab vedotin (LV) with pembrolizumab in patients with triple-negative breast cancer. It will find out what side effects happen when participants get these two drugs. A side effect is anything the drugs do besides treating cancer. Pembrolizumab is a drug that can be used to treat triple-negative breast cancer. The trial will also find out if these drugs work to treat this type of cancer. Participants in this study have metastatic breast cancer. This means the cancer has spread to other parts of the body.

The primary goal of this study is to evaluate the combination of LV, which targets LIV-1- expressing tumor cells, with the checkpoint inhibitor pembrolizumab for patients with unresectable locally-advanced or metastatic triple-negative breast cancer. These two drugs act through distinct and possibly complementary modes of action.

This is a single-arm, open-label, multicenter trial. Patients given LV and pembrolizumab during dose escalation will be monitored for frequency of dose-limiting toxicities to determine a recommended doses for expansion cohorts. In addition to safety measures, objective response rate, progression-free survival, overall survival, and other efficacy outcomes will be assessed.

Inclusion Criteria:

• Metastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)

  • Part D only: Tumor tissue PD-L1 Combined Positive Score <10 expression.

• Have not previously received cytotoxic therapy for the treatment of unresectable locally-advanced breast cancer or metastatic breast cancer

• At least 6 months since prior treatment with curative intent and recurrence

• At least 1 tumor 10mm in diameter or greater OR lymph node of at least 15 mm in short axis

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• Able to provide biopsy tissue for biomarker analysis

• Meet baseline laboratory data criteria

Exclusion Criteria:

• Prior immune-oncology therapy
• Pre-existing neuropathy of at least Grade 2
• History of carcinomatous meningitis or active central nervous system (CNS) metastases. Patients are eligible if CNS metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 4 weeks prior to enrollment. Patients must be off corticosteroids.
• Received prior radiotherapy within 2 weeks of start of study treatment or have not adequately recovered from prior radiotherapy
• Active autoimmune disease requiring systemic treatment within the past 2 years
• History of interstitial lung disease
• Current pneumonitis or history of pneumonitis requiring steroids