A Safety Study of SGN-LIV1A in Breast Cancer Patients

Study Overview
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Brief Summary
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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.

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

Conditions
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HER2 Positive Breast Neoplasms, Hormone Receptor Positive Breast Neoplasms, Triple Negative Breast Neoplasms, HER2 Mutations Breast Neoplasms

Intervention / Treatment
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* Drug: ladiratuzumab vedotin
* Drug: Trastuzumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Monomethyl auristatin E, Antibody-drug conjugate, Drug therapy, Metastatic, LIV-1 protein, human, Trastuzumab, Ladiratuzumab vedotin, hLIV22-vcMMAE, Seattle Genetics