Unresectable Locally-Advanced or Metastatic Triple-Negative Breast Cancer MedDRA version: 20.0 Level: LLT Classification code 10072740 Term: Locally advanced breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: PT Classification code 10075566 Term: Triple negative breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT
Conditions
Interventions
Product Name: Ladiratuzumab vedotin
Product Code: SGN-LIV1A
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: ladiratuzumab vedotin
CAS Number: 1629760-29-7
Current Spon
Sponsors
Seattle Genetics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Metastatic or locally-advanced, histologically documented TNBC (absence of HER2, ER, and PR expression). 2. Have not previously received therapy for the treatment of unresectable LA/M breast cancer. 3. For patients previously treated with curative intent, at least 12 months must have elapsed between the completion of such treatment (e.g., date of primary breast tumor surgery or date of last adjuvant cytotoxic therapy administration, whichever occurred last) and first documented local or distant disease recurrence. 4. Measureable disease per computed tomography (CT) scan as defined in RECIST v1.1: at least 1 tumor lesion =10 mm in the longest diameter, or a lymph node =15 mm in short axis measurement. 5. Patients =18 years of age. 6. An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1. 7. Able to provide fresh tissue for biomarker analysis from a newly obtained core or excisional biopsy of a tumor lesion. 8. Meet baseline laboratory data criteria. 9. For patients of childbearing potential as defined in Section 4.3, the following stipulations apply: a. Must have a negative serum or urine pregnancy test b. Must agree not to try to become pregnant from the time of enrollment until at least 6 months after the final dose of study drug. 10. Patient must provide written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 58 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 14
Exclusion criteria
Exclusion criteria: 1. Prior treatment with SGN LIV1A. 2. Prior immuno-oncology therapy 3. Pre-existing neuropathy of Grade =2. 4. Radiographic evidence of central nervous system metastases. 5. History of leptomeningeal carcinomatosis. 6. Active infection requiring systemic treatment =7 days before dose of study drug. 7. Known to be positive for hepatitis B by surface antigen expression, active hepatitis C infection or a known history of being seropositive for HIV. 8. Active autoimmune disease that has required systemic treatment in past 2 years 9. History of interstitial lung disease. 10. Current pneumonitis, or history of (non-infectious, including radiation induced) pneumonitis that required steroids. 14. Has a diagnosis of immunodeficiency or is receiving steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. 15. Patients who are breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? Evaluate the safety and tolerability of the combination of SGN LIV1A and pembrolizumab in patients with locally-advanced or metastatic, triple-negative breast cancer (LA/M TNBC) ? Identify the recommended dose of SGN LIV1A in combination with pembrolizumab in patients with LA/M TNBC ? Evaluate confirmed objective response rate (ORR) as measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 of the combination of SGN LIV1A and pembrolizumab in patients with LA/M TNBC;Secondary Objective: ? Assess duration of response (DOR), disease control rate (DCR), and progression-free survival (PFS) as measured by RECIST v1.1 ? Assess overall survival (OS);Primary end point(s): ? Type, incidence, severity, seriousness, and relatedness of AEs ? Laboratory abnormalities ? Incidence of dose-limiting toxicity (DLT) ? Confirmed ORR as determined by the investigator according to RECIST v1.1;Timepoint(s) of evaluation of this end point: Safety evaluation including AEs, laboratory abnormalities and incidence of DLT: in Part A, the safety of combination treatment will be evaluated by the SMC prior to expansion of enrollment to evaluate treatment effect in Part B. After 6 patients have been followed through the end of the DLT period, or at the point that 2 or more patients experience a DLT, whichever comes first. In Part B, the SMC will continue to evaluate and monitor the safety of study drug throughout the study. It will convene as needed. - For confirmed ORR: Patients will be evaluated for response after every 2 cycles of treatment in the first 8 cycles, and after every fourth cycle thereafter. If clinically indicated, response evaluation may be preformed earlier at the discretion of the investigator. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? DOR as determined by RECIST v1.1 ? DCR as determined by RECIST v1.1. ? PFS as determined by RECIST v1.1 ? OS;Timepoint(s) of evaluation of this end point: - Response evaluation for confirmed DOR, DCR and PFS: Patients will be evaluated for response after every 2 cycles of treatment in the first 8 cycles, and after every fourth cycle thereafter. If clinically indicated, response evaluation may be preformed earlier at the discretion of the investigator. - OS status evaluation: All patients will be followed for survival until death or study closure, whichever occurs first. Patients will be followed every 12 weeks (±1 week). | — |
Countries
France, Germany, Italy, Spain, United States
Contacts
Public ContactMiguelle Doki-Thonon
PRA Health Sciences
Outcome results
None listed