Phase 2
Completed N=144
A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
Source: ClinicalTrials.gov NCT03280563 ↗Enrolled (actual)
144
Serious AEs
25.6%
Results posted
Nov 2025
Primary outcomePrimary: Stage 1: Percentage of Participants With Objective Response — 10.0; 10.0; 26.9; 16.7 percentage of participants
Summary
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Stage 1: Percentage of Participants With Objective Response |
10.0; 10.0; 26.9; 16.7; 6.7; 26.3 | — |
| SECONDARY Stage 1: Progression-free Survival (PFS) |
1.95; 3.15; 5.86; 2.28; 1.82; 6.28 | — |
| SECONDARY Stage 1: Clinical Benefit Rate (CBR) |
15.0; 26.7; 42.3; 16.7; 6.7; 42.1 | — |
| SECONDARY Stage 1: Overall Survival (OS) |
26.02; 26.48; 26.91; 10.91; 23.10; 26.71 | — |
| SECONDARY Stage 1: Percentage of Participants Event-free for OS at Month 18 |
63.91; 63.16; 81.61; NA; 75.76; 74.40 | — |
| SECONDARY Stage 1: Duration of Response (DOR) |
13.03; 5.88; 11.07; 4.40; 2.46; 13.36 | — |
| SECONDARY Stages 1 and 2: Number of Participants With Adverse Events (AEs) |
18; 28; 26; 6; 15; 39 | — |
| SECONDARY Stage 1: Plasma Concentration of Entinostat |
NA; 22.3; 2.12 | — |
| SECONDARY Stage 1: Plasma Concentration of Abemaciclib |
0.00417; 0.0581; 0.319; 0.108; 0.144 | — |
| SECONDARY Stage 1: Plasma Concentration of Ipatasertib |
0.0353; 0.0105; 0.154; 0.203; 0.447; 0.398 | — |
| SECONDARY Stage 1: Plasma Concentration of Fulvestrant |
0.0127; 0.0136; 0.0161; 0.0107; 0.0121 | — |
| SECONDARY Stage 2: Plasma Concentration of Fulvestrant |
0.0207; 0.00938; 0.0142; 0.0121; 0.0175; 0.0132 | — |
| SECONDARY Stage 2: Serum Concentration of Atezolizumab |
217; 128; 443; 160; 277; 167 | — |
| SECONDARY Stage 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab |
0; 0; 0 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT03280563). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.