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

NCT03310957 | Completed Phase 1 Results FDA Drug

• 4 other identifiers: SGNLVA-002KEYNOTE 7212017-002289-35MK-3475-721
• Study Type: interventional
• Target: 185
• Locations: 4 countries
• Sites: 50

Brief Summary

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.

Conditions

Triple Negative Breast Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (4)

• Duration of Response (DOR) Per RECIST v1.1

  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)

  From start of study treatment up to date of CR or PR or SD (maximum up to 30 months)

• Progression-Free Survival (PFS)

  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)

  From start of study treatment until the date of death, or censoring date, whichever came first (maximum up to 30 months)

Study Arms (1)

LV + pembrolizumab

EXPERIMENTAL

LV + pembrolizumab

Drug: ladiratuzumab vedotin; Drug: Pembrolizumab

Interventions

ladiratuzumab vedotin DRUG

Given into the vein (IV; intravenously)

Also known as: LV, SGN-LIV1A

LV + pembrolizumab

Pembrolizumab DRUG

IV infusion every 3 weeks

Also known as: KEYTRUDA®

LV + pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (50)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

Chao Family Comprehensive Cancer Center University of California Irvine

Orange, California, 92868, United States

Location

University of California Irvine - Newport

Orange, California, 92868, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

The Whittingham Cancer Center / Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

Helen F. Graham Cancer Center / Christiana Care Health Systems

Newark, Delaware, 19713, United States

Location

Miami Cancer Institute at Baptist Health, Inc.

Miami, Florida, 33176, United States

Location

AdventHealth Cancer Institute

Orlando, Florida, 32804, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Piedmont Cancer Institute

Atlanta, Georgia, 30309, United States

Location

Winship Cancer Institute / Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Ingalls Cancer Care / Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Cardinal Bernardin Cancer Center / Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Allina Health Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

Saint Luke's Cancer Institute LLC

Kansas City, Missouri, 64111, United States

Location

Summit Medical Group

Florham Park, New Jersey, 07932, United States

Location

New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Texas Oncology - DFW

Dallas, Texas, 75246, United States

Location

Texas Oncology - Houston Memorial City

Houston, Texas, 77024, United States

Location

Texas Oncology - San Antonio Medical Center Northeast

San Antonio, Texas, 78212, United States

Location

University of Virginia

Charlottesville, Virginia, 22903, United States

Location

Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109-1023, United States

Location

Gynakologisches Zentrum Bonn Friedensplatz

Bonn, Other, 53111, Germany

Location

Marien Hospital Bottrop

Bottrop, Other, 46236, Germany

Location

Stadtisches Klinikum Dessau

Dessau, Other, 06847, Germany

Location

Universitatsklinikum Erlangen

Erlangen, Other, 91054, Germany

Location

Kliniken Essen-Mitte - Evang. Huyssens-Stiftung

Essen, Other, 45136, Germany

Location

Rotkreuzklinikum Munich

Munich, Other, 80637, Germany

Location

Klinikum Rechts der Isar der Technischen Universitaet Muenchen

München, Other, 81675, Germany

Location

Klinikum der Universitat Munchen

München, 80337, Germany

Location

Pusan National University Hospital

Busan, Other, 49201, South Korea

Location

CHA Bundang Medical Center

Seongnam, Other, 13496, South Korea

Location

Korea Cancer Center Hospital

Seoul, Other, 01802, South Korea

Location

Seoul National University Hospital

Seoul, Other, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, Other, 03722, South Korea

Location

Samsung Medical Center

Seoul, Other, 06351, South Korea

Location

Complejo Hospitalario Universitario La Coruna

A Coruña, Other, 15006, Spain

Location

Hospital del Mar

Barcelona, Other, 08003, Spain

Location

Hospital Universitari Vall d'Hebron

Barcelona, Other, 08035, Spain

Location

Complejo Hospitalario de Jaen

Jaén, Other, 23007, Spain

Location

L'Institut Catala d'Oncologia

L'Hospitalet de Llobregat, Other, 08907, Spain

Location

MD Anderson Cancer Center - Madrid

Madrid, Other, 28033, Spain

Location

Hospital Ruber Internacional

Madrid, Other, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Other, 28041, Spain

Location

HM Centro Integral Oncologico Clara Campal

Madrid, Other, 28050, Spain

Location

Hospital Universitario Quironsalud Madrid

Pozuelo de Alarcón, Other, 28223, Spain

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

SGN-LIV1A; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Seagen Inc.

medinfo@seagen.com

(855) 473-2436

Study Officials

• Zejing Wang, MD, PhD

  Seagen Inc.

  STUDY DIRECTOR

• Kristel Apolinario, PharmD

  Seagen Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 11, 2017
• First Posted: October 16, 2017
• Study Start: February 27, 2018
• Primary Completion: September 30, 2024
• Study Completion: September 30, 2024
• Last Updated: December 12, 2025
• Results First Posted: December 12, 2025

Record last verified: 2025-12

Locations

KR (6); DE (8); US (26); ES (10)