Unresectable locally advanced or metastatic breast cancer (MBC). MedDRA version: 20.0 Level: PT Classification code 10065430 Term: HER-2 positive breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer
Conditions
Sponsors
F. Hoffmann-La Roche Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Age >=18 years - Archival tumor samples must be obtained from primary and/or metastatic sites - Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression - Human epidermal growth factor-2 positive breast cancer (BC) as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of >=2.0 for the number of HER2 gene copies to the number of chromosome 17 copies, prospectively tested by a Sponsor- designated central laboratory prior to enrollment. Both IHC and ISH assays will be performed; however, only one positive result is required for eligibility - Histologically or cytologically confirmed invasive BC incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic breast cancer - Prior treatment for BC in the adjuvant, unresectable locally advanced or metastatic settings which must include both, a taxane and trastuzumab (alone or in combination with another agent) - Progression must have occurred during or after most recent treatment for locally advanced BC/MBC or within 6 months after completing adjuvant therapy - Participants must have measurable disease that is evaluable as per RECIST v1.1 - Eastern Cooperative Oncology Group Performance Status of 0 or 1 - Adequate hematologic and end-organ function as evidenced by the following local laboratory results obtained within 2 weeks prior to the first study treatment (Cycle 1, Day 1): • Absolute neutrophil count >=1500 cells/microliter (µL) (without granulocyte-colony stimulating factor support) within 2 weeks prior to Cycle 1, Day 1 • Platelet count >=100,000/µL (without transfusion within 2 weeks prior to Cycle 1, Day 1) • Hemoglobin >=9.0 gram/deciliter (g/dL) • Albumin > 2.5 g/dL • Aspartate aminotransferase, alanine transaminase, and alkaline phosphatase = 30 millilitre/min - Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause - For women of childbearing potential, agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of trastuzumab emtansine or 5 months after the last dose of atezolizumab/placebo, whichever is later. Women must refrain from donating eggs during this same period. - For men, agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm that together result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose trastuzumab emtansine. 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 200
Exclusion criteria
Exclusion criteria: - Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death 1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents - Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1, except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria - Radiation therapy within 2 weeks prior to Cycle 1, Day 1 - History of exposure to the cumulative doses of anthracyclines - History of other malignancy within the previous 5 years - Cardiopulmonary dysfunction - Patients with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia - Current severe, uncontrolled systemic disease - Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment - Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus - Need for current chronic corticosteroid therapy - Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to randomization - Participants with known central nervous system disease - Leptomeningeal disease - Symptomatic pleural effusion, pericardial effusion, or ascites - Uncontrolled hypercalcemia (>1.5 millimol/litre ionized calcium or calcium > 12 milligram/dL or corrected serum calcium greater than the ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy - Current Grade >= 3 peripheral neuropathy - History of autoimmune disease and idiopathic pulmonary fibrosis - Prior allogeneic stem cell or solid organ transplantation - Active tuberculosis - Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study - Treatment with systemic immunostimulatory agents - Treatment with systemic corticosteroids or other systemic immunosuppressive medications - Breastfeeding, or intending to become pregnat during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of the combination of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo as measured by progression free survival (PFS) using Response Evaluation Criteria in Solid tumors (RECIST) v1.1.; Secondary Objective: • To evaluate the efficacy of the combination of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo as measured by overall survival (OS), objective response rate (ORR), and duration of response (DOR) using RECIST v1.1 • To evaluate the overall safety of trastuzumab emtansine in combination with atezolizumab compared with trastuzumab emtansine in combination with placebo • To characterize the pharmacokinetics of atezolizumab in the presence of trastuzumab emtansine and trastuzumab emtansine in the presence and absence of atezolizumab • To characterize the incidence of anti-therapeutic antibody (ATA) to atezolizumab and trastuzumab emtansine. ;Primary end point(s): PFS as determined by investigator’s tumor assessment.;Timepoint(s) of evaluation of this end point: Up to 40 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy : 1. OS as determined by investigator’s tumor assessment 2. ORR as determined by investigator’s tumor assessment 3. DOR as determined by investigator’s tumor assessment Safety: 4. Nature, frequency, severity, and timing of adverse events including cardiac, hepatic and pulmonary events 5. Clinical laboratory results during and following trastuzumab emtansine and atezolizumab administration Pharmacokinetic: 6. Serum concentration of trastuzumab emtansine 7. Serum concentration of total trastuzumab 8. Plasma concentration of Deacetyl Mercapto 1 oxopropyl maytansine (DM1) 9. Serum concentration of atezolizumab Immunogenicity: 10. Numbers and proportions of ATA-positive patients and ATA-negative patients during both the treatment and follow up phase. ; Timepoint(s) of evaluation of this end point: 1-5. Up to 40 months 6. Day (D)1 of Cycle (C)1, C2, C4, and Study treatment(ST)/early discontinuation visit(EDV) 7. D1 of C1, C2 and C4 8. D1 of C1 and C4 9-10. D1 of C1, C2, C3, C4 and C8; thereafter every 8 cycles on D1 C8D1, ST/ EDV, and 120D (+/-28D) after treatment completion or discontinuation. | — |
Countries
Australia, Canada, Germany, Italy, Korea, Republic of, Spain, Taiwan, United Kingdom, United States
Contacts
Public ContactTrial Information Support Line-TISL
F. Hoffmann-La Roche Ltd
Outcome results
None listed