NCT03280563

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 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)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 144 (actual)
• Sponsor: Hoffmann-La Roche · Industry
• Sex: Female
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Breast Neoplasms

Interventions

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

Timeline

• Start date: 2017-12-22
• Primary completion: 2024-09-26
• Completion: 2024-09-26
• First posted: 2017-09-12
• Last updated: 2025-11-10
• Results posted: 2025-11-10

Locations

22 sites across 3 countries: United States, Israel, South Korea

Regulatory

• FDA-regulated drug study