A Safety Study of SGN-LIV1A in Breast Cancer Patients

A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety and Tolerability of SGN-LIV1A in Patients With Metastatic Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Neoplasms; Hormone Receptor Positive Breast Neoplasms; HER2 Positive Breast Neoplasms; HER2 Mutations Breast Neoplasms
• Intervention / Treatment: Drug: ladiratuzumab vedotin; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 290
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama at Birmingham
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Pinnacle Oncology Hematology
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego / Moores Cancer Center
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute
    • San Francisco, California, United States, 94134
      • University of California at San Francisco
    • Santa Monica, California, United States, 90404
      • UCLA Medical Center / David Geffen School of Medicine
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Rocky Mountain Cancer Centers - Aurora
    • Fort Collins, Colorado, United States, 80528
      • Poudre Valley Health System (PVHS)
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale Cancer Center
    • Norwalk, Connecticut, United States, 06856
      • The Whittingham Cancer Center / Norwalk Hospital
  • Florida
    • Tampa, Florida, United States, 33612
      • H. Lee Moffitt Cancer Center and Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Simon Cancer Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Louisiana State University Health Sciences Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute / Wayne State University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Minneapolis, Minnesota, United States, 55407
      • Allina Health Cancer institute
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in St Louis
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Cancer Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weill Cornell Medicine
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center / Wake Forest University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • The Cleveland Clinic
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University / University Hospitals Cleveland Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology-Nashville/Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Texas Oncology - Baylor Sammons Cancer Center
    • New Braunfels, Texas, United States, 78130
      • Cancer Care Centers of South Texas - HOAST/Texas Oncology
  • Washington
    • Puyallup, Washington, United States, 98373
      • Northwest Medical Specialties
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance / University of Washington
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LV Dose Escalation	Drug: ladiratuzumab vedotin; LV will be given into the vein (IV; intravenously); Other Names: LV; SGN-LIV1A
Experimental: LV + Trastuzumab	Drug: ladiratuzumab vedotin; LV will be given into the vein (IV; intravenously); Other Names: LV; SGN-LIV1A; Drug: Trastuzumab; Trastuzumab will be given by IV every 3 weeks at a dose of 6 mg/kg (the first dose will be 8 mg/kg); Other Names: Herceptin
Experimental: LV Monotherapy; LV will be given at the recommended dose (at or below the monotherapy MTD determined in the LV dose escalation arm).	Drug: ladiratuzumab vedotin; LV will be 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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1.	Through 1 month following last dose; up to approximately 2 years
Duration of response (DOR)	DOR is defined as the time from start of the first documentation of objective tumor response (CR or PR) to the first documentation of tumor progression (clinical progression or progressive disease (PD) per RECIST v1.1).	Up to approximately 3 years
Progression-free survival (PFS)	PFS is defined as the time from start of study treatment to first documentation of tumor progression (clinical progression or PD per RECIST v1.1).	Up to approximately 8 years
Overall survival (OS)	OS is defined as the time from start of study treatment to date of death due to any cause.	Up to approximately 8 years
PFS relative to prior therapy	The PFS ratio is defined for each subject as the ratio of the current PFS and the PFS achieved on their most recent therapy where they experienced progression.	Up to approximately 8 years

Collaborators and Investigators

• Sponsor: Seagen Inc.
• Investigators: Study Director: Brandon Croft, PharmD, Seagen Inc.; Study Director: Zejing Wang, MD, PhD, Seagen Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2013
• Primary Completion (Actual): February 4, 2023
• Study Completion (Actual): February 4, 2023

Study Registration Dates

• First Submitted: October 21, 2013
• First Submitted That Met QC Criteria: October 21, 2013
• First Posted (Estimate): October 25, 2013

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Drug therapy; Metastatic; Seattle Genetics; Trastuzumab; Monomethyl auristatin E; Antibody-drug conjugate; LIV-1 protein, human; Ladiratuzumab vedotin; hLIV22-vcMMAE
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Site; Breast Diseases; Neoplasms; Breast Neoplasms; Triple Negative Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: SGNLVA-001

Drug and device information, study documents

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