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Sponsor: Hoffmann-La Roche
Conditions: Breast Neoplasms
Interventions: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Bevacizumab, Entinostat, Exemestane, Fulvestrant
Countries: United States, Israel, South Korea
This study is designed to evaluate the efficacy, safety, and pharmacokinetics of several immunotherapy-based combination treatments in participants with inoperable locally advanced or metastatic HR-positive, HER2-negative breast cancer who have progressed during or following treatment with a cyclin-dependent kinase (CDK) 4/6 inhibitor in the first- or second-line setting, such as palbociclib, ribociclib, or abemaciclib. The study will be performed in two stages. During Stage 1, participants will be randomized to fulvestrant (control) or an atezolizumab-containing doublet or triplet combination. Those who experience disease progression, loss of clinical benefit, or unacceptable toxicity may be eligible to receive a new triplet combination treatment in Stage 2 until loss of clinical benefit or unacceptable toxicity. New treatment arms may be added and/or existing treatment arms may be closed during the course of the study on the basis of ongoing clinical efficacy and safety as well as the current treatments available.
Sex: FEMALE
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Inclusion Criteria for Both Stages: * Measurable disease per RECIST v1.1 * Adequate hematologic and end organ function * Disease progression during or after first- or second-line hormonal therapy with CDK4/6 inhibitor Inclusion Criteria for Stage 1: * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Metastatic or inoperable, locally advanced, histologically or cytologically confirmed invasive HR-positive HER2-negative breast cancer * Recommended for endocrine therapy, and cytotoxic chemotherapy not indicated at study entry * Recurrence or progression following most recent systemic breast cancer therapy * Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease * Postmenopausal according to protocol-defined criteria * Life expectancy \>3 months * Available tumor specimen for determination of PD-L1 status Inclusion Criteria for Stage 2: * ECOG performance status of 0-2 * Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen Exclusion Criteria for Both Stages: * Significant or uncontrolled comorbid disease as specified in the protocol * Uncontrolled tumor-related pain * Autoimmune disease except for stable/controlled hypothyroidism, Type 1 diabetes mellitus, or certain dermatologic conditions * Positive human immunodeficiency virus test * Active hepatitis B or C * Active tuberculosis * Severe infection within 4 weeks and/or antibiotics within 2 weeks prior to study treatment * Prior allogeneic stem cell or solid organ transplantation * History of malignancy other than breast cancer within 2 years prior to screening except those with negligible risk of metastasis/death * History of or known hypersensitivity to study drug or excipients * For patients entering Stage 2, recovery from all immunotherapy-related adverse events to Grade 1 or better or to baseline at the time of consent Exclusion Criteria for Stage 1: * Prior fulvestrant or cytotoxic chemotherapy for metastatic breast cancer, or certain other agents as specified in the protocol * Unresolved AEs from prior anti-cancer therapy * Eligibility only for the control arm * Prior treatment with inhibitors as specified in the protocol Exclusion Criteria for Stage 2: * Unacceptable toxicity with atezolizumab during Stage 1 * Uncontrolled cardiovascular disease or coagulation disorder, including use of anticoagulants as specified in the protocol * Significant abdominal or intestinal manifestations within 6 months prior to treatment * Grade 2 or higher proteinuria
- Birmingham, Alabama, United States
- San Francisco, California, United States
- Stanford, California, United States
- Torrance, California, United States
- West Hills, California, United States
- Marietta, Georgia, United States
- Baltimore, Maryland, United States
- New York, New York, United States
- Charlotte, North Carolina, United States
- Portland, Oregon, United States
- Harrisburg, Pennsylvania, United States
- Philadelphia, Pennsylvania, United States
- Pittsburgh, Pennsylvania, United States
- Nashville, Tennessee, United States
- Haifa, Israel
- Jerusalem, Israel
- Petah Tikva, Israel
- Ramat Gan, Israel
- Tel Aviv, Israel
- Gyeonggi-do, South Korea
- Seoul, South Korea
- Seoul, South Korea