Clinical trial NCT01969643: A Safety Study of SGN-LIV1A in Breast Cancer Patients
Official title: A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of SGN-LIV1A in Patients With Metastatic Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HER2 Positive Breast Neoplasms
Hormone Receptor Positive Breast Neoplasms
Triple Negative Breast Neoplasms
HER2 Mutations Breast Neoplasms
Keywords: Monomethyl auristatin E
Antibody-drug conjugate
Drug therapy
Metastatic
LIV-1 protein, human
Trastuzumab
Ladiratuzumab vedotin
hLIV22-vcMMAE
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2013-10-25
Enrollment: 290
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the safety and tolerability of ladiratuzumab vedotin (LV) in patients with metastatic breast cancer. LV will be given alone or in combination with trastuzumab.


Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed diagnosis of breast cancer with radiographic evidence of incurable, unresectable, locally advanced or metastatic disease (LA/MBC)
* One of the following:

  * Part A: Triple-negative disease (ER/PR/HER2-negative) and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting; or ER-positive and/or PR-positive/HER2-negative disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting and are no longer a candidate for hormonal therapy (not enrolling new patients);
  * Part B: Combination Arm: HER2-positive disease and received at least 2 prior cytotoxic regimens in the incurable, unresectable, LA/MBC setting (not enrolling new patients);
  * Part C: Triple-negative disease and received 2-4 prior non-hormonally-directed therapies in the MBC setting (not enrolling new patients);
  * Part D and Part E (dose-expansion cohort): Triple-negative disease and received 1 prior non-hormonally-directed or cytotoxic therapy in the MBC setting; or
  * Part E: HR+(ER-positive and/or PR-positive)/HER2-negative disease who are chemotherapy-eligible and not considered a candidate for further hormonal therapy. Must have received no more than 1 prior non-hormonally-directed or cytotoxic therapy in the LA/MBC setting.
* Part F: All of the following:

  * Triple negative breast cancer
  * No prior cytotoxic chemotherapy for unresectable locally advanced or metastatic stage disease
  * Tumor tissue PD-L1 expression CPS \<10 expression
* Parts A, B, C, and D: Newly obtained or archived tumor tissue biopsy, must be collected for central pathology determination of LIV-1 expression
* Parts E and F: Archival or fresh baseline tumor sample is required.
* Measurable disease
* Eastern Cooperative Oncology Group performance status 0 or 1
* Combination Arm: adequate heart function

Exclusion Criteria:

* Pre-existing neuropathy Grade 2 or higher
* Parts A, B, C, and D: Cerebral/meningeal disease that is related to the underlying malignancy and has not been definitively treated. Parts E and F: Known or suspected cerebral/meningeal metastasis that has not been definitively treated.
* Prior treatment with LV or prior treatment with an MMAE-containing therapy
* Combination Arm: hypersensitivity to trastuzumab

Primary outcomes:
measure: Incidence of adverse events
timeFrame: Through 1 month following last dose; up to approximately 2 years
measure: Incidence of laboratory abnormalities
timeFrame: Through 1 month following last dose; up to approximately 2 years
measure: Incidence of dose-limiting toxicity (DLT)
timeFrame: Through 3 weeks after first dose
Secondary outcomes:
measure: Blood concentrations of LV and metabolites
timeFrame: Through 3 weeks after dosing; up to approximately 2 years
measure: Incidence of antitherapeutic antibodies
timeFrame: Through 1 month following last dose; up to approximately 2 years
measure: Objective response rate (ORR)
timeFrame: Through 1 month following last dose; up to approximately 2 years
measure: Duration of response (DOR)
timeFrame: Up to approximately 3 years
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 8 years
measure: Overall survival (OS)
timeFrame: Up to approximately 8 years
measure: PFS relative to prior therapy
timeFrame: Up to approximately 8 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Scottsdale
country: United States
facility: Pinnacle Oncology Hematology
state: Arizona
city: La Jolla
country: United States
facility: UC San Diego / Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Santa Monica
country: United States
facility: UCLA Medical Center / David Geffen School of Medicine
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers - Aurora
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Health System (PVHS)
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Norwalk
country: United States
facility: The Whittingham Cancer Center / Norwalk Hospital
state: Connecticut
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: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Simon Cancer Center
state: Indiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute / Wayne State University
state: Michigan
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University in St Louis
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center / Wake Forest University
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University / University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Tennessee Oncology-Nashville/Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Baylor Sammons Cancer Center
state: Texas
city: New Braunfels
country: United States
facility: Cancer Care Centers of South Texas - HOAST/Texas Oncology
state: Texas
city: Puyallup
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance / University of Washington
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Seagen Inc.
name: Brandon Croft, PharmD
role: STUDY_DIRECTOR
affiliation: Seagen Inc.
name: Zejing Wang, MD, PhD
role: STUDY_DIRECTOR
References: