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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Triple Negative Breast Neoplasms

Intervention / Treatment
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* Drug: ladiratuzumab vedotin
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LV + pembrolizumab<br>LV + pembrolizumab | Drug: ladiratuzumab vedotin<br>* Given into the vein (IV; intravenously)<br>* Other names: SGN-LIV1A;Drug: Pembrolizumab<br>* IV infusion every 3 weeks<br>* Other names: KEYTRUDA®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed objective response rate | Confirmed ORR as determined by investigator according to RECIST v 1.1 | Up to 18 weeks following last dose; approximately 1 year | 
| Incidence of adverse events |  | Through 1 month following last dose; approximately 10 months | 
| Incidence of laboratory abnormalities |  | Through 1 month following last dose; approximately 10 months | 
| Incidence of dose-limiting toxicities |  | Through 1 month following last dose; approximately 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response | DOR as determined by investigator according to RECIST v 1.1 | Up to 2.5 years following last dose | 
| Disease control rate | Proportion of patients with complete response (CR), partial response (PR), or stable disease (SD) as determined by investigator according to RECIST v 1.1 | Up to 2.5 years following last dose | 
| Progression-free survival | PFS as determined by investigator according to RECIST v 1.1 | Up to 2.5 years following last dose | 
| Overall survival | OS is defined as the time from start of study treatment to date of death due to any cause. | Up to 2.5 years following last dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Breast carcinoma, Triple negative breast cancer, Locally-advanced breast cancer, Metastatic breast cancer, Tumors, breast, Breast tumors, pembrolizumab, LIV-1 protein, human, Ladiratuzumab vedotin, hLIV22-vcMMAE, Seattle Genetics