A Safety Study of SGN-LIV1A in Breast Cancer Patients

Triple Negative Breast Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01969643
• Other study ID #: SGNLVA-001
• Status: Completed
• Phase: Phase 1
• Start date: October 22, 2013
• Est. completion date: February 4, 2023

Study information

• Verified date: March 2023
• Source: Seagen Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: February 4, 2023
• Est. primary completion date: February 4, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• ladiratuzumab vedotin
LV will be given into the vein (IV; intravenously)
• 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)

Locations

Country	Name	City	State
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Piedmont Cancer Institute	Atlanta	Georgia
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	University of Maryland	Baltimore	Maryland
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Case Western Reserve University / University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	The Cleveland Clinic	Cleveland	Ohio
United States	Texas Oncology - Baylor Sammons Cancer Center	Dallas	Texas
United States	Karmanos Cancer Institute / Wayne State University	Detroit	Michigan
United States	Poudre Valley Health System (PVHS)	Fort Collins	Colorado
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	UC San Diego / Moores Cancer Center	La Jolla	California
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Cedars Sinai Medical Center / Samuel Oschin Comprehensive Cancer Institute	Los Angeles	California
United States	Allina Health Cancer Institute	Minneapolis	Minnesota
United States	University of Minnesota	Minneapolis	Minnesota
United States	West Virginia University	Morgantown	West Virginia
United States	Tennessee Oncology-Nashville/Sarah Cannon Research Institute	Nashville	Tennessee
United States	Cancer Care Centers of South Texas - HOAST/Texas Oncology	New Braunfels	Texas
United States	Yale Cancer Center	New Haven	Connecticut
United States	Louisiana State University Health Sciences Center	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	The Whittingham Cancer Center / Norwalk Hospital	Norwalk	Connecticut
United States	Oregon Health and Science University	Portland	Oregon
United States	Northwest Medical Specialties	Puyallup	Washington
United States	Mayo Clinic Rochester	Rochester	Minnesota
United States	Washington University in St Louis	Saint Louis	Missouri
United States	University of California at San Francisco	San Francisco	California
United States	UCLA Medical Center / David Geffen School of Medicine	Santa Monica	California
United States	Pinnacle Oncology Hematology	Scottsdale	Arizona
United States	Seattle Cancer Care Alliance / University of Washington	Seattle	Washington
United States	Swedish Cancer Institute	Seattle	Washington
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	Wake Forest Baptist Medical Center / Wake Forest University	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Seagen Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Incidence of laboratory abnormalities	To be summarized using descriptive statistics.	Through 1 month following last dose; up to approximately 2 years
Primary	Incidence of dose-limiting toxicity (DLT)		Through 3 weeks after first dose
Secondary	Blood concentrations of LV and metabolites		Through 3 weeks after dosing; up to approximately 2 years
Secondary	Incidence of antitherapeutic antibodies		Through 1 month following last dose; up to approximately 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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