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A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
Not Recruiting
Trial ID: NCT03280563
Purpose
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.
Official Title
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Hormone Receptor-Positive HER2-Negative Breast Cancer (MORPHEUS-HR+ Breast Cancer)
Stanford Investigator(s)
Melinda L. Telli, M.D.
Professor of Medicine (Oncology)
Eligibility
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
Intervention(s):
drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody
drug: Bevacizumab
drug: Entinostat
drug: Exemestane
drug: Fulvestrant
drug: Ipatasertib
drug: Tamoxifen
drug: Abemaciclib
Not Recruiting
Contact Information
Stanford University
School of Medicine
300 Pasteur Drive
Stanford,
CA
94305
Annabel (Grace) Castaneda
650-498-7977