Breast NeoplasmsPhase 1/2MORPHEUS HR+BCNCT03280563
A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer
A Phase 1/2 study testing Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Bevacizumab and Entinostat in people with Breast Neoplasms, run by Hoffmann-La Roche at 22 sites in 3 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms
- What is being tested?
- Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Bevacizumab and Entinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 144 participants
- Where
- 22 sitesin 3 countries
- Study dates
- 22 Dec 2017to 26 Sep 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
- 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
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- 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
- ECOG performance status of 0-2
- Ability to initiate treatment within 3 months after disease progression or unacceptable toxicity on a Stage 1 regimen
Who cannot join
- 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
Show all 19Show fewer
- 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
- 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
- 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
Trial locations and contacts
22 sites in 3 countries.
22 sites in 3 countries
United States14 sites
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21231
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Levine Cancer Institute
Charlotte, North Carolina, 28204
UPMC Pinnacle Health System
Harrisburg, Pennsylvania, 17102
Northwest Georgia Oncology Centers PC - Marietta
Marietta, Georgia, 30060
Sarah Cannon Research Institute / Tennessee Oncology
Nashville, Tennessee, 37203
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107
Univ of Pittsburgh Sch of Med
Pittsburgh, Pennsylvania, 15213
Providence Cancer Center
Portland, Oregon, 97231
UCSF Helen Diller Family CCC
San Francisco, California, 94158
Stanford Cancer Institute
Stanford, California, 94305-5456
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
Torrance, California, 90502
Wellness Oncology and Hematology - Main Office
West Hills, California, 91307
Israel5 sites
Rambam Medical Center
Haifa, 3109601
Shaare Zedek Medical Center
Jerusalem, 9103102
Rabin Medical Center-Beilinson Campus
Petah Tikva, 4941492
Sheba Medical Center
Ramat Gan, 5262100
Tel Aviv Sourasky Medical Center
Tel Aviv, 64239
South Korea3 sites
National Cancer Center
Gyeonggi-do, 10408
Seoul National University Hospital
Seoul, 03080
University of Ulsan College of Medicine - Asan Medical Center
Seoul, 05505
About this study
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)
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.
- Conditions
- Breast Neoplasms
- Being tested
- Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Bevacizumab, Entinostat, Exemestane, Fulvestrant
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibodyDrug
Also called Tecentriq
Atezolizumab will be given as 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle. This regimen will apply to all arms except when given with entinostat in Stage 1, or exemestane or tamoxifen in Stage 2, in which atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle.
BevacizumabDrug
Also called Avastin
Bevacizumab will be given as 10 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 15 of each 28-day cycle in the regimen containing fulvestrant. When given with exemestane or tamoxifen, bevacizumab will be given as 15 mg/kg via IV infusion on Day 1 of each 21-day cycle.
EntinostatDrug
Entinostat will be given as 5 mg orally once a week on Days 1, 8 and 15 of each 21-day cycle.
ExemestaneDrug
Exemestane will be given as 25 mg orally QD in each 21-day cycle.
FulvestrantDrug
Fulvestrant will be given as 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle.
IpatasertibDrug
Ipatasertib will be given as 400 mg orally QD on Days 1-21 of each 28-day cycle.
TamoxifenDrug
Tamoxifen will be given as 20 mg orally QD in each 21-day cycle.
AbemaciclibDrug
Abemaciclib will be given as 150mg twice daily during each 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Stage 1: Fulvestrant | Active comparator | Participants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1. Receives: Drug: Fulvestrant |
| Stage 1: Atezolizumab + Entinostat | Experimental | Participants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Entinostat |
| Stage 1: Atezolizumab + Fulvestrant | Experimental | Participants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant |
| Stage 1: Atezolizumab + Ipatasertib | Experimental | Participants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Ipatasertib |
| Stage 1: Atezolizumab + Ipatasertib + Fulvestrant | Experimental | Participants will receive triplet combination treatment with atezolizumab plus ipatasertib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant; Drug: Ipatasertib |
| Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy | Experimental | Those who progress or experience unacceptable toxicity during treatment in Stage 1 may be eligible to enter Stage 2. Participants will receive triplet combination therapy with atezolizumab plus bevacizumab plus one of three endocrine therapies (fulvestrant, exemestane, or tamoxifen) selected by the physician. Treatment in Stage 2 will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Bevacizumab; Drug: Exemestane; Drug: Fulvestrant; Drug: Tamoxifen |
| Stage 1: Mandatory On-Treatment Biopsy | Experimental | For experimental combination arms that demonstrate clinical activity during the preliminary phase, the Sponsor may open enrollment into a separate mandatory on-treatment biopsy cohort for that combination. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Entinostat; Drug: Fulvestrant; Drug: Ipatasertib; Drug: Abemaciclib |
| Stage 1: Atezolizumab + Abemaciclib + Fulvestrant | Experimental | Participants will receive triplet combination treatment with atezolizumab plus abemaciclib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Receives: Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody; Drug: Fulvestrant; Drug: Abemaciclib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Stage 1: Percentage of Participants With Objective Response
Objective response rate (ORR) was defined as the percentage of participants with an objective response of complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) that have a reduction in short axis to < 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off to the nearest whole number.
Measured: Up to 50.4 months
Secondary outcomes (13)
Stage 1: Progression-free Survival (PFS)
PFS was defined as the time from randomization to the date of the first recorded occurrence of PD or death from any cause (whichever occurred first) in Stage 1, as determined by the investigator according to RECIST v1.1. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in the study including baseline in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥ 5 mm. Participants who did not have documented PD or death, PFS was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for PFS.
Measured: From randomization to the first occurrence of PD or death (up to 51.9 months)
Stage 1: Clinical Benefit Rate (CBR)
CBR was defined as the percentage of participants with stable disease (SD) ≥ 24 weeks or with confirmed CR or PR, as determined by the investigator according to RECIST v1.1. SD was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD. CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) having a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥ 5 mm. Percentages have been rounded off to the nearest whole number.
Measured: Up to 51.9 months
Stage 1: Overall Survival (OS)
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier method was used to estimate the median for OS.
Measured: From randomization to death (up to 62.2 months)
Stage 1: Percentage of Participants Event-free for OS at Month 18
OS was defined as the time from randomization to death from any cause. Participants who were still alive at the time of OS analysis were censored at the last date they were known to be alive. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for OS at Month 18. Percentages have been rounded off to the nearest whole number.
Measured: At Month 18
Stage 1: Duration of Response (DOR)
DOR was defined as the time from the first occurrence of a documented objective response (CR or PR) to the first date of recorded PD or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) having a reduction in short axis to < 10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum in study including baseline in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥ 5 mm. Participants who did not have documented PD or death, DOR was censored at the day of the last tumor assessment. The Kaplan-Meier method was used to estimate the median for DOR.
Measured: From first occurrence of a documented OR to the first date of recorded PD or death (up to 50.4 months)
Stages 1 and 2: Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation subject administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
SAE = serious adverse events; AESIs = adverse events of special interest.
Measured: From baseline until 30 days (for AEs) or 135 days (for SAEs & AESIs) after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurred first (Stage 1: up to 52 months; Stage 2: up to 21.7 months)
Stage 1: Plasma Concentration of Entinostat
Measured: Predose on Day 1 of Cycles 1 and 2; 2-4 hours postdose on Day 1 Cycle 1 (Cycle length = 21 days)
Stage 1: Plasma Concentration of Abemaciclib
Measured: Predose on Day 1 of Cycles 1, 2 and 3, and on Day 15 Cycle 1; 4-8 hours postdose on Day 1 Cycle 1 (Cycle length = 28 days)
Stage 1: Plasma Concentration of Ipatasertib
Measured: Predose and Postdose at 1 Hour, 2 Hour, 4 Hour, and 6 Hour on Day 15 Cycle 1; Post dose at 1-3 Hour on Day 15 Cycle 3 (Cycle length = 28 days)
Stage 1: Plasma Concentration of Fulvestrant
Measured: Predose on Day 1 of Cycle 2 and Cycle 3 (Cycle length = 28 days)
Stage 2: Plasma Concentration of Fulvestrant
Nominal time restarted to 0 at Stage 2. PK data for Stage was analyzed and reported for the subgroups [crossover arms (Stage 1 to Stage 2)] only.
Measured: Predose on Day 1 of Cycles 2 and 3 (Cycle length = 21 days)
Stage 2: Serum Concentration of Atezolizumab
Nominal time restarted to 0 at Stage 2; RO5541267 = atezolizumab. PK data for Stage was analyzed and reported for the subgroups [crossover arms (Stage 1 to Stage 2)] only.
Measured: Predose on Day 1 of Cycles 1, 2, 3, 4, 8 and 12; 30 minutes (mins) postdose on Day 1 Cycle 1; postdose on Day 120 and Treatment Discontinuation Visit (Cycle length = 21 days)
Stage 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Participants who received atezolizumab were considered to be treatment-emergent ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following atezolizumab exposure (treatment-induced ADA response), or if they were ADA-positive at baseline and the titer of one or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be treatment-emergent ADA-negative if they were ADA-negative or were missing data at baseline and all post-baseline samples were negative, or if they were ADA-positive at baseline but did not have any post-baseline samples with a titer that was at least 0.60 t.u. greater than the titer of the baseline sample (treatment unaffected). Participants with a positive post-baseline sample has been reported here.
Measured: Post-baseline (up to approximately 134 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2017
- Study start22 Dec 2017
- Primary completion26 Sep 2024
- Study completion26 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03280563
- Sponsor's protocol ID
- CO39611
- Other IDs
- 2017-000335-14, 2017
- Acronym
- MORPHEUS HR+BC
- Status last verified
- Oct 2025
- First submitted
- 11 Sep 2017
- Last updated
- 10 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03280563
- Acronym / sponsor ID
- MORPHEUS HR+BC / CO39611
- Conditions
- Breast Neoplasms
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Hoffmann-La RocheIndustry (pharma, biotech, devices)
- Study start
- 22 Dec 2017 (actual)
- Primary completion
- 26 Sep 2024 (actual)
- Study completion
- 26 Sep 2024 (actual)
- First posted
- 12 Sep 2017 (actual)
- Results
- Posted 10 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Stage 1: Fulvestrant | Active comparator | Drug: FulvestrantParticipants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1. |
| Stage 1: Atezolizumab + Entinostat | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: EntinostatParticipants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Stage 1: Atezolizumab + Fulvestrant | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: FulvestrantParticipants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Stage 1: Atezolizumab + Ipatasertib | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: IpatasertibParticipants will receive doublet combination treatment with atezolizumab plus ipatasertib until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib. |
| Stage 1: Atezolizumab + Ipatasertib + Fulvestrant | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: Fulvestrant, Drug: IpatasertibParticipants will receive triplet combination treatment with atezolizumab plus ipatasertib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. Prior to enrollment into this arm, the first 6 participants in the study will complete a safety run-in with atezolizumab plus ipatasertib. |
| Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: Bevacizumab, Drug: Exemestane, Drug: Fulvestrant, Drug: TamoxifenThose who progress or experience unacceptable toxicity during treatment in Stage 1 may be eligible to enter Stage 2. Participants will receive triplet combination therapy with atezolizumab plus bevacizumab plus one of three endocrine therapies (fulvestrant, exemestane, or tamoxifen) selected by the physician. Treatment in Stage 2 will continue until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
| Stage 1: Mandatory On-Treatment Biopsy | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: Entinostat, Drug: Fulvestrant, Drug: Ipatasertib, Drug: AbemaciclibFor experimental combination arms that demonstrate clinical activity during the preliminary phase, the Sponsor may open enrollment into a separate mandatory on-treatment biopsy cohort for that combination. |
| Stage 1: Atezolizumab + Abemaciclib + Fulvestrant | Experimental | Drug: Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Drug: Fulvestrant, Drug: AbemaciclibParticipants will receive triplet combination treatment with atezolizumab plus abemaciclib plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibodyAlso: TecentriqAtezolizumab will be given as 840 milligrams (mg) via intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle. This regimen will apply to all arms except when given with entinostat in Stage 1, or exemestane or tamoxifen in Stage 2, in which atezolizumab will be given as 1200 mg via IV infusion on Day 1 of each 21-day cycle. | Drug | Stage 1: Atezolizumab + Abemaciclib + Fulvestrant, Stage 1: Atezolizumab + Entinostat, Stage 1: Atezolizumab + Fulvestrant, Stage 1: Atezolizumab + Ipatasertib, Stage 1: Atezolizumab + Ipatasertib + Fulvestrant, Stage 1: Mandatory On-Treatment Biopsy, Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy |
| BevacizumabAlso: AvastinBevacizumab will be given as 10 milligrams per kilogram (mg/kg) via IV infusion on Days 1 and 15 of each 28-day cycle in the regimen containing fulvestrant. When given with exemestane or tamoxifen, bevacizumab will be given as 15 mg/kg via IV infusion on Day 1 of each 21-day cycle. | Drug | Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy |
| EntinostatEntinostat will be given as 5 mg orally once a week on Days 1, 8 and 15 of each 21-day cycle. | Drug | Stage 1: Atezolizumab + Entinostat, Stage 1: Mandatory On-Treatment Biopsy |
| ExemestaneExemestane will be given as 25 mg orally QD in each 21-day cycle. | Drug | Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy |
| FulvestrantFulvestrant will be given as 500 mg intramuscularly on Days 1 and 15 of Cycle 1 and thereafter on Day 1 of each 28-day cycle. | Drug | Stage 1: Atezolizumab + Abemaciclib + Fulvestrant, Stage 1: Atezolizumab + Fulvestrant, Stage 1: Atezolizumab + Ipatasertib + Fulvestrant, Stage 1: Fulvestrant, Stage 1: Mandatory On-Treatment Biopsy, Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy |
| IpatasertibIpatasertib will be given as 400 mg orally QD on Days 1-21 of each 28-day cycle. | Drug | Stage 1: Atezolizumab + Ipatasertib, Stage 1: Atezolizumab + Ipatasertib + Fulvestrant, Stage 1: Mandatory On-Treatment Biopsy |
| TamoxifenTamoxifen will be given as 20 mg orally QD in each 21-day cycle. | Drug | Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy |
| AbemaciclibAbemaciclib will be given as 150mg twice daily during each 28-day cycle. | Drug | Stage 1: Atezolizumab + Abemaciclib + Fulvestrant, Stage 1: Mandatory On-Treatment Biopsy |
Primary outcome
Stage 1: Percentage of Participants With Objective Response
Time frame: Up to 50.4 months
Objective response rate (ORR) was defined as the percentage of participants with an objective response of complete response (CR) or partial response (PR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1). CR was defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) that have a reduction in short axis to < 10 millimeters (mm). PR was defined as at least a 30% decrease in the sum of diameters (SOD) of all target lesions, taking as reference the baseline SOD, in the absence of CR. Participants with missing or no response assessments were classified as non-responders. Percentages have been rounded off to the nearest whole number.
13 secondary outcomes
Stage 1: Progression-free Survival (PFS)
Time frame: From randomization to the first occurrence of PD or death (up to 51.9 months)
Stage 1: Clinical Benefit Rate (CBR)
Time frame: Up to 51.9 months
Stage 1: Overall Survival (OS)
Time frame: From randomization to death (up to 62.2 months)
Stage 1: Percentage of Participants Event-free for OS at Month 18
Time frame: At Month 18
Stage 1: Duration of Response (DOR)
Time frame: From first occurrence of a documented OR to the first date of recorded PD or death (up to 50.4 months)
Stages 1 and 2: Number of Participants With Adverse Events (AEs)
Time frame: From baseline until 30 days (for AEs) or 135 days (for SAEs & AESIs) after the last dose of study treatment or until initiation of new systemic anti-cancer therapy, whichever occurred first (Stage 1: up to 52 months; Stage 2: up to 21.7 months)
Stage 1: Plasma Concentration of Entinostat
Time frame: Predose on Day 1 of Cycles 1 and 2; 2-4 hours postdose on Day 1 Cycle 1 (Cycle length = 21 days)
Stage 1: Plasma Concentration of Abemaciclib
Time frame: Predose on Day 1 of Cycles 1, 2 and 3, and on Day 15 Cycle 1; 4-8 hours postdose on Day 1 Cycle 1 (Cycle length = 28 days)
Stage 1: Plasma Concentration of Ipatasertib
Time frame: Predose and Postdose at 1 Hour, 2 Hour, 4 Hour, and 6 Hour on Day 15 Cycle 1; Post dose at 1-3 Hour on Day 15 Cycle 3 (Cycle length = 28 days)
Stage 1: Plasma Concentration of Fulvestrant
Time frame: Predose on Day 1 of Cycle 2 and Cycle 3 (Cycle length = 28 days)
Stage 2: Plasma Concentration of Fulvestrant
Time frame: Predose on Day 1 of Cycles 2 and 3 (Cycle length = 21 days)
Stage 2: Serum Concentration of Atezolizumab
Time frame: Predose on Day 1 of Cycles 1, 2, 3, 4, 8 and 12; 30 minutes (mins) postdose on Day 1 Cycle 1; postdose on Day 120 and Treatment Discontinuation Visit (Cycle length = 21 days)
Stage 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab
Time frame: Post-baseline (up to approximately 134 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Trials study director
Hoffmann-La Roche
22 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody, Bevacizumab and Entinostat in people with Breast Neoplasms, run by Hoffmann-La Roche at 22 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in United States, Israel, South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Percentage of Participants With Objective Response (time frame: Up to 50.4 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2025; AzTrials last refreshed its copy on 1 Nov 2026.