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

• Status: Completed
• Trial end date: 2020-02-06
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hoffmann-La Roche
• Treatments: Ado-Trastuzumab Emtansine; Antibodies, Monoclonal; Atezolizumab; Maytansine; Trastuzumab

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