A Safety Study of SGN-LIV1A in Breast Cancer Patients

• ClinicalTrials.gov Identifier: NCT01969643
• Recruitment Status: Completed
• First Posted: October 25, 2013
• Last Update Posted: March 7, 2023
• Sponsor: Seagen Inc.
• Information provided by (Responsible Party): Seagen Inc.

Tracking Information

• First Submitted Date: October 21, 2013
• First Posted Date: October 25, 2013
• Last Update Posted Date: March 7, 2023
• Actual Study Start Date: October 22, 2013
• Actual Primary Completion Date: February 4, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2021)

• Incidence of adverse events [ Time Frame: Through 1 month following last dose; up to approximately 2 years ]
  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.
• Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose; up to approximately 2 years ]
  To be summarized using descriptive statistics.
• Incidence of dose-limiting toxicity (DLT) [ Time Frame: Through 3 weeks after first dose ]

Original Primary Outcome Measures (submitted: October 21, 2013)

• Incidence of adverse events [ Time Frame: Through 1 month following last dose ]
• Incidence of laboratory abnormalities [ Time Frame: Through 1 month following last dose ]

Current Secondary Outcome Measures (submitted: April 2, 2021)

• Blood concentrations of LV and metabolites [ Time Frame: Through 3 weeks after dosing; up to approximately 2 years ]
• Incidence of antitherapeutic antibodies [ Time Frame: Through 1 month following last dose; up to approximately 2 years ]
• Objective response rate (ORR) [ Time Frame: Through 1 month following last dose; up to approximately 2 years ]
  ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1.
• Duration of response (DOR) [ Time Frame: Up to approximately 3 years ]
  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).
• Progression-free survival (PFS) [ Time Frame: Up to approximately 8 years ]
  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).
• Overall survival (OS) [ Time Frame: Up to approximately 8 years ]
  OS is defined as the time from start of study treatment to date of death due to any cause.
• PFS relative to prior therapy [ Time Frame: Up to approximately 8 years ]
  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.

Original Secondary Outcome Measures (submitted: October 21, 2013)

• Blood concentrations of SGN-LIV1A and metabolites [ Time Frame: Through 3 weeks after dosing ]
• Incidence of antitherapeutic antibodies [ Time Frame: Through 1 month following last dose ]
• Objective response rate [ Time Frame: Through 1 month following last dose ]
• Duration of response [ Time Frame: Up to approximately 3 years ]
• Progression-free survival [ Time Frame: Up to approximately 3 years ]
• Progression-free survival relative to prior therapy [ Time Frame: Up to approximately 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HER2 Positive Breast Neoplasms
• Hormone Receptor Positive Breast Neoplasms
• Triple Negative Breast Neoplasms
• HER2 Mutations Breast Neoplasms

Intervention

• 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 Name: Herceptin

Study Arms

• Experimental: LV Dose Escalation
  Intervention: Drug: ladiratuzumab vedotin
• Experimental: LV + Trastuzumab
  Interventions:

  • Drug: ladiratuzumab vedotin
  • Drug: Trastuzumab
• Experimental: LV Monotherapy
  LV will be given at the recommended dose (at or below the monotherapy MTD determined in the LV dose escalation arm).
  Intervention: Drug: ladiratuzumab vedotin

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 19, 2022): 290
• Original Estimated Enrollment (submitted: October 21, 2013): 51
• Actual Study Completion Date: February 4, 2023
• Actual Primary Completion Date: February 4, 2023 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01969643
• Other Study ID Numbers: SGNLVA-001
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Seagen Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Seagen Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Seagen Inc.
• Verification Date: March 2023