A Safety Study of SGN-LIV1A in Breast Cancer Patients

NCT01969643 | Completed Phase 1 FDA Drug

• 1 other identifier: SGNLVA-001
• Study Type: interventional
• Target: 290
• Locations: 1 country
• Sites: 38

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.

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

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  An AE is any untoward medical occurrence in a patient or clinical investigational subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment.

  Through 1 month following last dose; up to approximately 2 years

• Incidence of laboratory abnormalities

  To be summarized using descriptive statistics.

  Through 1 month following last dose; up to approximately 2 years

• Incidence of dose-limiting toxicity (DLT)

  Through 3 weeks after first dose

Secondary Outcomes (7)

• Blood concentrations of LV and metabolites

  Through 3 weeks after dosing; up to approximately 2 years

• Incidence of antitherapeutic antibodies

  Through 1 month following last dose; up to approximately 2 years

• Objective response rate (ORR)

  Through 1 month following last dose; up to approximately 2 years

• Duration of response (DOR)

  Up to approximately 3 years

• Progression-free survival (PFS)

  Up to approximately 8 years

Study Arms (3)

LV Dose Escalation

EXPERIMENTAL

Drug: ladiratuzumab vedotin

LV + Trastuzumab

EXPERIMENTAL

Drug: ladiratuzumab vedotin; Drug: Trastuzumab

LV Monotherapy

EXPERIMENTAL

LV will be given at the recommended dose (at or below the monotherapy MTD determined in the LV dose escalation arm).

Drug: ladiratuzumab vedotin

Interventions

ladiratuzumab vedotin DRUG

LV will be given into the vein (IV; intravenously)

Also known as: LV, SGN-LIV1A

LV + Trastuzumab; LV Dose Escalation; LV Monotherapy

Trastuzumab DRUG

Trastuzumab will be given by IV every 3 weeks at a dose of 6 mg/kg (the first dose will be 8 mg/kg)

Also known as: Herceptin

LV + Trastuzumab

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seagen Inc.: lead

Study Sites (38)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

UC San Diego / Moores Cancer Center

La Jolla, California, 92093, United States

Location

Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute

Los Angeles, California, 90048, United States

Location

University of California at San Francisco

San Francisco, California, 94134, United States

Location

UCLA Medical Center / David Geffen School of Medicine

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers - Aurora

Aurora, Colorado, 80012, United States

Location

Poudre Valley Health System (PVHS)

Fort Collins, Colorado, 80528, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06520, United States

Location

The Whittingham Cancer Center / Norwalk Hospital

Norwalk, Connecticut, 06856, 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

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

Location

Indiana University Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Louisiana State University Health Sciences Center

New Orleans, Louisiana, 70112, United States

Location

University of Maryland

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Karmanos Cancer Institute / Wayne State University

Detroit, Michigan, 48201, United States

Location

Allina Health Cancer Institute

Minneapolis, Minnesota, 55407, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University in St Louis

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87131, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Wake Forest Baptist Medical Center / Wake Forest University

Winston-Salem, North Carolina, 27157, United States

Location

Case Western Reserve University / University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

The Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Tennessee Oncology-Nashville/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Texas Oncology - Baylor Sammons Cancer Center

Dallas, Texas, 75246, United States

Location

Cancer Care Centers of South Texas - HOAST/Texas Oncology

New Braunfels, Texas, 78130, United States

Location

Northwest Medical Specialties

Puyallup, Washington, 98373, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Seattle Cancer Care Alliance / University of Washington

Seattle, Washington, 98109, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Neoplasm Metastasis

Interventions

SGN-LIV1A; Trastuzumab

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Brandon Croft, PharmD

  Seagen Inc.

  STUDY DIRECTOR

• Zejing Wang, MD, PhD

  Seagen Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2013
• First Posted: October 25, 2013
• Study Start: October 22, 2013
• Primary Completion: February 4, 2023
• Study Completion: February 4, 2023
• Last Updated: March 7, 2023

Record last verified: 2023-03

Locations

US (38)