HER2 Mutations Breast Neoplasms, HER2 Positive Breast Neoplasms, Hormone Receptor Positive Breast Neoplasms, Triple Negative Breast Neoplasms
Conditions
Keywords
Monomethyl auristatin E, Antibody-drug conjugate, Drug therapy, Metastatic, LIV-1 protein, human, Trastuzumab, Ladiratuzumab vedotin, hLIV22-vcMMAE, Seattle Genetics
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.
Interventions
LV will be given into the vein (IV; intravenously)
DRUGTrastuzumab
Trastuzumab will be given by IV every 3 weeks at a dose of 6 mg/kg (the first dose will be 8 mg/kg)
Sponsors
Seagen Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | 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 | Through 1 month following last dose; up to approximately 2 years | To be summarized using descriptive statistics. |
| Incidence of dose-limiting toxicity (DLT) | Through 3 weeks after first dose | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of response (DOR) | 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) | 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). |
| Blood concentrations of LV and metabolites | Through 3 weeks after dosing; up to approximately 2 years | — |
| PFS relative to prior therapy | 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. |
| Overall survival (OS) | Up to approximately 8 years | OS is defined as the time from start of study treatment to date of death due to any cause. |
| 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 | ORR is defined as the proportion of patients with complete response (CR) or partial response (PR) per RECIST v1.1. |
Countries
United States
Outcome results
None listed