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
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Atezolizumab; Trastuzumab emtansine; Placebo
Intervention description: Atezolizumab 1200 mg IV infusion; Trastuzumab emtansine 3.6 mg/kg IV infusion; Placebo matched to atezolizumab
Intervention MeSH terms: Trastuzumab; Atezolizumab; Ado-Trastuzumab Emtansine; Maytansine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 202.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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