Clinical Trials /

A Safety Study of SGN-LIV1A in Breast Cancer Patients

NCT01969643

Description:

This study will examine the safety and tolerability of SGN-LIV1A (ladiratuzumab vedotin) in patients with metastatic breast cancer. SGN-LIV1A will be given alone or in combination with trastuzumab.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: SGNLVA-001
  • NCT ID: NCT01969643

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
SGN-LIV1ASGN-LIV1A Dose Escalation
TrastuzumabHerceptinSGN-LIV1A + Trastuzumab

Purpose

This study will examine the safety and tolerability of SGN-LIV1A (ladiratuzumab vedotin) in patients with metastatic breast cancer. SGN-LIV1A will be given alone or in combination with trastuzumab.

Trial Arms

NameTypeDescriptionInterventions
SGN-LIV1A Dose EscalationExperimental
  • SGN-LIV1A
SGN-LIV1A + TrastuzumabExperimental
  • SGN-LIV1A
  • Trastuzumab
SGN-LIV1AExperimentalSGN-LIV1A will be given at the recommended dose (at or below the monotherapy MTD determined in the SGN-LIV1A dose escalation arm).
  • SGN-LIV1A

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.

          -  Parts A, B, C, and D: Newly obtained tumor tissue biopsy and archived tumor tissue, if
             available, must be collected for central pathology determination of LIV-1 expression

          -  Part E: Archival baseline tumor sample is required; a fresh biopsy sample may be
             submitted in place of an archival sample if medically feasible.

          -  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. Part E: Known or suspected
             cerebral/meningeal metastasis that has not been definitively treated.

          -  Prior treatment with SGN-LIV1A or prior treatment with an MMAE-containing therapy

          -  Combination Arm: hypersensitivity to trastuzumab
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Through 1 month following last dose; up to approximately 2 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Blood concentrations of SGN-LIV1A and metabolites
Time Frame:Through 3 weeks after dosing; up to approximately 2 years
Safety Issue:
Description:
Measure:Incidence of antitherapeutic antibodies
Time Frame:Through 1 month following last dose; up to approximately 2 years
Safety Issue:
Description:
Measure:Objective response rate (ORR)
Time Frame:Through 1 month following last dose; up to approximately 2 years
Safety Issue:
Description:ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1.
Measure:Duration of response (DOR)
Time Frame:Up to approximately 3 years
Safety Issue:
Description: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).
Measure:Progression-free survival (PFS)
Time Frame:Up to approximately 8 years
Safety Issue:
Description: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).
Measure:Overall survival (OS)
Time Frame:Up to approximately 8 years
Safety Issue:
Description:OS is defined as the time from start of study treatment to date of death due to any cause.
Measure:PFS relative to prior therapy
Time Frame:Up to approximately 8 years
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Seattle Genetics, Inc.

Trial Keywords

  • Breast cancer
  • Monomethyl auristatin E
  • Antibody-drug conjugate
  • Drug therapy
  • Metastatic
  • LIV-1 protein, human
  • Trastuzumab
  • Ladiratuzumab vedotin
  • hLIV22-vcMMAE

Last Updated

November 30, 2019