A Study of Multiple Immunotherapy-Based Treatment Combinations in Hormone Receptor (HR)-Positive Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Breast Cancer

Conditions

• Breast Neoplasms

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab (MPDL3280A), an engineered anti-programmed death-ligand 1 (PD-L1) antibody — DRUG
  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.
• Bevacizumab — DRUG
  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.
• Entinostat — DRUG
  Entinostat will be given as 5 mg orally once a week on Days 1, 8 and 15 of each 21-day cycle.
• Exemestane — DRUG
  Exemestane will be given as 25 mg orally QD in each 21-day cycle.
• Fulvestrant — DRUG
  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.
• Ipatasertib — DRUG
  Ipatasertib will be given as 400 mg orally QD on Days 1-21 of each 28-day cycle.
• Tamoxifen — DRUG
  Tamoxifen will be given as 20 mg orally QD in each 21-day cycle.
• Abemaciclib — DRUG
  Abemaciclib will be given as 150mg twice daily during each 28-day cycle.

Study Details

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.

Key Dates

Start date

Dec 22, 2017

Status verified

Oct 2025

Primary completion

Sep 26, 2024

Completion

Sep 26, 2024

Study Design

Enrollment

144 participants (actual)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Active Comparator: Stage 1: Fulvestrant
  Participants will receive fulvestrant until unacceptable toxicity or disease progression according to RECIST v1.1.
• Experimental: Stage 1: Atezolizumab + Entinostat
  Participants will receive doublet combination treatment with atezolizumab plus entinostat until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
• Experimental: Stage 1: Atezolizumab + Fulvestrant
  Participants will receive doublet combination treatment with atezolizumab plus fulvestrant until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
• Experimental: Stage 1: Atezolizumab + Ipatasertib
  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.
• Experimental: Stage 1: Atezolizumab + Ipatasertib + Fulvestrant
  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.
• Experimental: Stage 2: Atezolizumab + Bevacizumab + Endocrine Therapy
  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.
• Experimental: Stage 1: Mandatory On-Treatment Biopsy
  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.
• Experimental: Stage 1: Atezolizumab + Abemaciclib + Fulvestrant
  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.

Primary Outcome Measure

Stage 1: Percentage of Participants With Objective Response [ Time Frame: Up to 50.4 months ]

Locations (14)

Related coverage on Hipa.ai

• Atezolizumab Triplets Show Improved Response, PFS in HR+/HER2- Breast Cancer
  Atezolizumab · Nov 10, 2025 · ClinicalTrials.gov

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