Clinical trial NCT03310957: Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
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
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2017-10-16
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Confirmed objective response rate
timeFrame: Up to 18 weeks following last dose; approximately 1 year
measure: Incidence of adverse events
timeFrame: Through 1 month following last dose; approximately 10 months
measure: Incidence of laboratory abnormalities
timeFrame: Through 1 month following last dose; approximately 10 months
measure: Incidence of dose-limiting toxicities
timeFrame: Through 1 month following last dose; approximately 10 months
Secondary outcomes:
measure: Duration of response
timeFrame: Up to 2.5 years following last dose
measure: Disease control rate
timeFrame: Up to 2.5 years following last dose
measure: Progression-free survival
timeFrame: Up to 2.5 years following last dose
measure: Overall survival
timeFrame: Up to 2.5 years following last dose
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center University of California Irvine
state: California
city: Orange
country: United States
facility: University of California Irvine - Newport
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Norwalk
country: United States
facility: The Whittingham Cancer Center / Norwalk Hospital
state: Connecticut
city: Newark
country: United States
facility: Helen F. Graham Cancer Center / Christiana Care Health Systems
state: Delaware
city: Miami
country: United States
facility: Miami Cancer Institute at Baptist Health, Inc.
state: Florida
city: Orlando
country: United States
facility: AdventHealth Cancer Institute
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Piedmont Cancer Institute
state: Georgia
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University School of Medicine
state: Georgia
city: Harvey
country: United States
facility: Ingalls Cancer Care / Ingalls Memorial Hospital
state: Illinois
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center / Loyola University Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Kansas City
country: United States
facility: Saint Luke's Cancer Institute LLC
state: Missouri
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC)/Hillman Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Texas Oncology - DFW
state: Texas
city: Houston
country: United States
facility: Texas Oncology - Houston Memorial City
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Medical Center Northeast
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center / Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Bonn
country: Germany
facility: Gynakologisches Zentrum Bonn Friedensplatz
state: Other
city: Bottrop
country: Germany
facility: Marien Hospital Bottrop
state: Other
city: Dessau
country: Germany
facility: Stadtisches Klinikum Dessau
state: Other
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
state: Other
city: Essen
country: Germany
facility: Kliniken Essen-Mitte - Evang. Huyssens-Stiftung
state: Other
city: Muenchen
country: Germany
facility: Klinikum Rechts der Isar der Technischen Universitaet Muenchen
state: Other
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen
state: Other
city: Munich
country: Germany
facility: Rotkreuzklinikum Munich
state: Other
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
state: Other
city: Seongnam
country: Korea, Republic of
facility: CHA Bundang Medical Center
state: Other
city: Seoul
country: Korea, Republic of
facility: Korea Cancer Center Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Other
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Other
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Other
city: Barcelona
country: Spain
facility: Hospital del Mar
state: Other
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
state: Other
city: Jaen
country: Spain
facility: Complejo Hospitalario de Jaen
state: Other
city: L'Hospitalet de Llobregat
country: Spain
facility: L'Institut Catala d'Oncologia
state: Other
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario La Coruna
state: Other
city: Madrid
country: Spain
facility: MD Anderson Cancer Center - Madrid
state: Other
city: Madrid
country: Spain
facility: Hospital Ruber Internacional
state: Other
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Other
city: Madrid
country: Spain
facility: HM Centro Integral Oncologico Clara Campal
state: Other
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quironsalud Madrid
state: Other
Study officials:
affiliation: Seagen Inc.
name: Zejing Wang, MD, PhD
role: STUDY_DIRECTOR
affiliation: Seagen Inc.
name: Kristel Apolinario, PharmD
role: STUDY_DIRECTOR
References: