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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Neoplasms
• Intervention / Treatment: Drug: Pembrolizumab; Drug: ladiratuzumab vedotin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • München, Germany, 80337
    • Klinikum der Universität München
  • Other
    • Bonn, Other, Germany, 53111
      • Gynakologisches Zentrum Bonn Friedensplatz
    • Bottrop, Other, Germany, 46236
      • Marien Hospital Bottrop
    • Dessau, Other, Germany, 06847
      • Städtisches Klinikum Dessau
    • Erlangen, Other, Germany, 91054
      • Universitätsklinikum Erlangen
    • Essen, Other, Germany, 45136
      • Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
    • Munich, Other, Germany, 80637
      • Rotkreuzklinikum Munich
    • München, Other, Germany, 81675
      • Klinikum Rechts der Isar der Technischen Universitaet Muenchen
• South Korea
  • Other
    • Busan, Other, South Korea, 49201
      • Pusan National University Hospital
    • Seongnam, Other, South Korea, 13496
      • CHA Bundang Medical Center
    • Seoul, Other, South Korea, 03722
      • Severance Hospital, Yonsei University Health System
    • Seoul, Other, South Korea, 06351
      • Samsung Medical Center
    • Seoul, Other, South Korea, 03080
      • Seoul National University Hospital
    • Seoul, Other, South Korea, 01802
      • Korea Cancer Center Hospital
• Spain
  • Other
    • A Coruña, Other, Spain, 15006
      • Complejo Hospitalario Universitario La Coruna
    • Barcelona, Other, Spain, 08003
      • Hospital del Mar
    • Barcelona, Other, Spain, 08035
      • Hospital Universitari Vall d'Hebron
    • Jaén, Other, Spain, 23007
      • Complejo Hospitalario de Jaén
    • L'Hospitalet de Llobregat, Other, Spain, 08907
      • L'Institut Catala d'Oncologia
    • Madrid, Other, Spain, 28041
      • Hospital Universitario 12 de Octubre
    • Madrid, Other, Spain, 28050
      • HM Centro Integral Oncológico Clara Campal
    • Madrid, Other, Spain, 28033
      • MD Anderson Cancer Center - Madrid
    • Madrid, Other, Spain, 28034
      • Hospital Ruber Internacional
    • Pozuelo de Alarcón, Other, Spain, 28223
      • Hospital Universitario Quironsalud Madrid
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center University of California Irvine
    • Orange, California, United States, 92868
      • University of California Irvine - Newport
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
  • Connecticut
    • Norwalk, Connecticut, United States, 06856
      • The Whittingham Cancer Center / Norwalk Hospital
  • Delaware
    • Newark, Delaware, United States, 19713
      • Helen F. Graham Cancer Center / Christiana Care Health Systems
  • Florida
    • Miami, Florida, United States, 33176
      • Miami Cancer Institute at Baptist Health, Inc.
    • Orlando, Florida, United States, 32804
      • AdventHealth Cancer Institute
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute / Emory University School of Medicine
    • Atlanta, Georgia, United States, 30309
      • Piedmont Cancer Institute
  • Illinois
    • Harvey, Illinois, United States, 60426
      • Ingalls Cancer Care / Ingalls Memorial Hospital
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center / Loyola University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health Cancer Institute
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Saint Luke's Cancer Institute LLC
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - DFW
    • Houston, Texas, United States, 77024
      • Texas Oncology - Houston Memorial City
    • San Antonio, Texas, United States, 78212
      • Texas Oncology - San Antonio Medical Center Northeast
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia
  • Washington
    • Seattle, Washington, United States, 98109-1023
      • Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. SAEs was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. TEAEs were defined as newly occurring (not present at baseline) or worsened after first dose of investigational product within 30 days after last dose date or within 90 days for SAE. AEs included SAEs and all non-SAEs.	From start of study treatment up to 30 days and up to 90 days post last dose for AEs and SAEs respectively (maximum exposure to any study treatment = 27 months; follow-up: AEs = maximum up to 28 months; SAEs = maximum up to 30 months)
Number of Participants With Treatment Related TEAEs and SAEs	An AE was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. SAEs was defined as any untoward medical occurrence that, at any dose, meets one or more of the criteria: death, life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, congenital anomaly or birth defect and other medically significant events. AEs included SAEs and all non-SAEs. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. AEs were defined as treatment emergent if they were newly occurring or worsened following study treatment. Relatedness to study drug was assessed by the investigator.	From start of study treatment up to 30 days and up to 90 days post last dose for AEs and SAEs respectively (maximum exposure to any study treatment = 27 months; follow-up: AEs = maximum up to 28 months; SAEs = maximum up to 30 months)
Number of Participants With AEs of Grade <3 and Grade >=3 Per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 4.03	An AE was any untoward medical occurrence in a study participant administered a medicinal product and which did not necessarily have a causal relationship with the study treatment. AEs severities were graded using the NCI CTCAE v4.03; where Grade 1= mild AE, Grade 2= moderate AE, Grade 3= severe AE, and Grade 4= life-threatening consequences; urgent intervention indicated, Grade 5= indicated death related to AE.	From start of study treatment up to 30 days for AEs (maximum exposure to any study treatment = 27 months; follow-up: AEs = maximum up to 28 months)
Number of Participants With Maximum Post-Baseline Laboratory Toxicity Grade (0 to 4) in Any Hematology Parameter	In this outcome measure, number of participants with maximum post-baseline laboratory toxicity grade in any hematology parameter are reported. As per NCI-CTCAE v4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, and Grade 4= life-threatening consequences; urgent intervention indicated; Grade 0 = within normal limits. Baseline was defined as most recent non-missing lab result before first dose. Hematology parameters evaluated: hemoglobin, leukocytes, lymphocytes, neutrophils and platelets.	Post-baseline up to 30 days after last dose (maximum exposure to any study intervention was 27 months; follow-up = maximum up to 28 months)
Number of Participants With Maximum Post-Baseline Laboratory Toxicity Grade (0 to 4) in Any Serum Chemistry Parameter	In this outcome measure, number of participants with maximum post-baseline laboratory toxicity grade in any serum chemistry parameters are reported. As per NCI-CTCAE v4.03: Grade 1= mild, Grade 2= moderate, Grade 3= severe, and Grade 4= life-threatening consequences; urgent intervention indicated; Grade 0 = within normal limits. Baseline was defined as most recent non-missing lab result before first dose. Serum chemistry parameters evaluated: alanine aminotransferase, albumin, alkaline phosphatase, amylase, aspartate aminotransferase, bilirubin, calcium corrected for albumin, calcium- ionized, creatinine, gamma glutamyl transferase, glucose, lipase, phosphate, potassium, sodium and urate. In this outcome measure, only those grades as rows are reported which had at least one participant for at least 1 reporting group.	Post-baseline up to 30 days after last dose (maximum exposure to any study intervention was 27 months; follow-up = maximum up to 28 months)
Number of Participants With Dose Limiting Toxicities (DLT): Part A and Part C	DLT : hematologic and/or non-hematologic AE specified in protocol that is considered related to SGN-LIV or the combination and cannot be attributed to pembrolizumab alone including: any clinically significant, non-hematologic AE>= Grade 3 according to NCI CTCAE v4.03, Grade 3 febrile neutropenia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia associated with clinically significant bleeding that required medical intervention, Grade 4 anemia unrelated to underlying disease, discontinuation during Cycle 1 due to treatment-related toxicity/ inability to receive all 3 doses of SGN-LIV (Days 1, 8, and 15) as participant not met dosing criteria (Part C only)prolonged delay (>2 weeks) in initiating Cycle 2 due to treatment-related toxicity and Grade 5 event (death).	Cycle 1 (up to 21 days)
ORR as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v)1.1	ORR was defined as the percentage of participants with confirmed complete response (CR) or partial response (PR) according to RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: >=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Kaplan Meier method was used for analysis.	From start of study treatment up to date of confirmed CR or PR (maximum up to 30 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR) Per RECIST v1.1	DOR = time from first documentation of objective response (subsequently confirmed) per investigator to first documentation of disease progression, or death due to any cause, whichever came first. CR: disappearance of all target lesions. Any pathological lymph nodes (reduction in short axis to <10 mm). PR: >=30% decrease in sum of diameters of target lesions, taking reference baseline sum diameters. Progression: at least a 20% increase in sum of diameters of target lesions, reference smallest sum on study (includes baseline sum if that is smallest on study). In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions. Kaplan-Meier method used for DOR evaluation. DOR was only calculated for subgroup of participants who achieved a confirmed CR or PR.	From the date of first CR or PR until the date of the first documentation of progression or death, or censoring date, whichever came first (maximum up to 30 months)
Disease Control Rate (DCR)	DCR was defined as percentage of participants with CR, PR, or stable disease (SD) per RECIST v1.1. CR: disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10 mm. PR: >=30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression, taking as reference the smallest sum diameters while on study. Progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference smallest sum on study (this includes baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. Appearance of one or more new lesions. Clopper-Pearson method was used for 95% confidence interval.	From start of study treatment up to date of CR or PR or SD (maximum up to 30 months)
Progression-Free Survival (PFS)	PFS was defined as the time from start of study treatment to first documentation of disease progression based upon the disease assessment per RECISTv1.1 or clinical progression, or to death due to any cause, whichever came first. Progression: at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 0.5 cm. The appearance of one or more new lesions. Kaplan-Meier method was used for PFS evaluation.	From start of study treatment until the date of the first documentation of progression or death, or censoring date, whichever came first (maximum up to 30 months)
Overall Survival (OS)	OS was defined as the time from start of study treatment to date of death due to any cause. In the absence of confirmation of death, OS was censored at the last date the participant was known to be alive. Kaplan-Meier method was used for OS evaluation.	From start of study treatment until the date of death, or censoring date, whichever came first (maximum up to 30 months)

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Zejing Wang, MD, PhD, Seagen Inc.; Study Director: Kristel Apolinario, PharmD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 27, 2018
• Primary Completion (Actual): September 30, 2024
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: October 11, 2017
• First Submitted That Met QC Criteria: October 11, 2017
• First Posted (Actual): October 16, 2017

Study Record Updates

• Last Update Posted (Estimated): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Breast cancer; Metastatic breast cancer; Breast tumors; Seattle Genetics; pembrolizumab; Triple negative breast cancer; Breast carcinoma; LIV-1 protein, human; Ladiratuzumab vedotin; hLIV22-vcMMAE; Locally-advanced breast cancer; Tumors, breast
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunoconjugates; SGN-LIV1A; pembrolizumab
• Other Study ID Numbers: SGNLVA-002; KEYNOTE 721 (Other Identifier: Merck Sharp & Dohme LLC); 2017-002289-35 (EudraCT Number); MK-3475-721 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No