a study to evaluate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with human epidermal growth factor-2 (her2) positive locally advanced or metastatic breast cancer (bc) who received prior trastuzumab and taxane based therapy

Conditions: Metastatic Breast Cancer

Summary: this phase ii, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with her2-positive locally advanced or metastatic bc who have received prior trastuzumab and taxane based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.


Eligibility criteria:
inclusion criteria: * 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 * her-2 positive bc as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (\>=) 2.0 for the number of her2 gene copies to the number of chromosome 17 copies * histologically or cytologically confirmed invasive bc: incurable, unresectable, locally advanced bc previously treated with multimodality therapy or metastatic bc * 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/metastatic bc 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 * 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 * use of highly effective method of contraception as defined by the protocol 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, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, stage i uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence * cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites * participants 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 (\>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids) * 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 greater than (\>) 2 weeks prior to randomization * participants with known central nervous system disease * leptomeningeal disease * history of autoimmune disease * 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 within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization * treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial * participants who are breastfeeding, or intending to become pregnant during the study