A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Breast Cancer (MORPHEUS-BREAST CANCER)
3 other identifiers
interventional
316
5 countries
31
Brief Summary
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with breast cancer. The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, or modify the patient population. Cohort 1 will focus on participants with inoperable, locally advanced or metastatic, estrogen receptor-positive (ER+), HER2-negative breast cancer who had disease progression during or following treatment with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i; e.g., palbociclib, ribociclib, abemaciclib) in the first- or second-line setting. Cohort 2 will focus on inoperable, locally advanced or metastatic, ER+, HER2-positive breast cancer with previous progression to standard-of-care anti-HER2 therapies, of which one was a trastuzumab-and-taxane-based systemic therapy (including in the early setting if recurrence occurred within 6 months of finishing adjuvant therapy) and one was a HER2-targeting antibody-drug conjugate (ADC; e.g., ado-trastuzumab emtansine or trastuzumab-deruxtecan) or a HER2-targeting tyrosine kinase inhibitor (TKI; e.g., tucatinib, lapatinib, pyrotinib, or neratinib). Cohort 3 will focus on inoperable, locally advanced or metastatic, ER+, HER2-negative, PIK3CA-mutated breast cancer with resistance to adjuvant endocrine therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jun 2021
Longer than P75 for phase_1
31 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 15, 2021
CompletedFirst Posted
Study publicly available on registry
March 17, 2021
CompletedStudy Start
First participant enrolled
June 22, 2021
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 30, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 30, 2029
April 13, 2026
April 1, 2026
7.9 years
March 15, 2021
April 10, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of Participants with Objective Response, Defined as a Complete or Partial Response, as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
From Baseline until disease progression (up to 6 years)
Number of Participants with Adverse Events, Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI CTCAE v5.0)
From Baseline until 30 days after the last dose of study drug (up to 6 years)
Secondary Outcomes (5)
Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1
From randomization to the date of the first recorded occurrence of disease progression or death from any cause, whichever occurs first (up to 6 years)
Disease Control Rate, Defined as the Percentage of Participants with Stable Disease for ≥12 Weeks or a Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1
From Baseline until disease progression (up to 6 years)
Clinical Benefit Rate, Defined as the Percentage of Participants with Stable Disease for ≥24 Weeks or with Confirmed Complete or Partial Response, as Determined by the Investigator According to RECIST v1.1
From Baseline until disease progression (up to 6 years)
Overall Survival
From randomization to death from any cause (up to 6 years)
Duration of Response, as Determined by the Investigator According to RECIST v1.1
From first occurrence of a document objective response to the first date of recorded disease progression or death from any cause, whichever occurs first (up to 6 years)
Study Arms (16)
Cohort 1: Giredestrant Monotherapy
ACTIVE COMPARATORCohort 1: Giredestrant + Abemaciclib
EXPERIMENTALCohort 1: Giredestrant + Ipatasertib
EXPERIMENTALCohort 1: Giredestrant + Inavolisib
EXPERIMENTALCohort 1: Giredestrant + Ribociclib
EXPERIMENTALCohort 1: Giredestrant + Everolimus
EXPERIMENTALCohort 1: Giredestrant + Samuraciclib
EXPERIMENTALCohort 1: Giredestrant + Atezolizumab
EXPERIMENTALCohort 1: Giredestrant + Abemaciclib + Atezolizumab
EXPERIMENTALCohort 1: Giredestrant + Inavolisib (ESR1m enriched)
EXPERIMENTALESR1m stands for estrogen receptor mutation.
Cohort 2: Giredestrant + PH FDC SC
ACTIVE COMPARATORCohort 2: Giredestrant + PH FDC SC + Abemaciclib
EXPERIMENTALCohort 2: Giredestrant + PH FDC SC + Palbociclib
EXPERIMENTALCohort 3: Giredestrant + Inavolisib + Palbociclib
EXPERIMENTALCohort 3: Giredestrant + Inavolisib + Abemaciclib
EXPERIMENTALCohort 3: Giredestrant + Inavolisib + Ribociclib
EXPERIMENTALInterventions
150 mg orally twice a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression
10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression
125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression
840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.
30 milligrams (mg) orally once a day (during each 28-day cycle or 21-day cycle, depending on the regimen) until unacceptable toxicity or disease progression
On Day 1 of Cycle 1 (1 cycle is 21 days), pertuzumab and trastuzumab fixed-dose combination for subcutaneous use (PH FDC SC) will be administered SC as a fixed dose formulation of 1200 mg pertuzumab, 600 mg trastuzumab, and 30,000 units hyaluronidase. On Day 1 of Cycles 2 and beyond, PH FDC SC will be administered SC once every 21 days as a fixed dose of 600 mg pertuzumab, 600 mg trastuzumab, and 20,000 units hyaluronidase.
Eligibility Criteria
You may qualify if:
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- Documented estrogen receptor-positive (ER+) tumor
- Patients for whom endocrine therapy is recommended and treatment with cytotoxic chemotherapy is not indicated at time of entry into the study, as per national or local treatment guidelines
- Radiologic/objective evidence of recurrence or progression after the most recent systemic therapy for breast cancer
- Disease progression during or after first- or second-line hormonal therapy for locally advanced or metastatic disease (note: at least one line of therapy must have contained a CDK4/6i administered for a minimum of 8 weeks prior to disease progression.)
- Postmenopausal status for women
- Life expectancy ≥3 months
- Availability of a representative tumor specimen that is suitable for biomarker evaluation via central testing
- Prior fulvestrant therapy is allowed
- Stages 1 and 2: Measurable disease (at least one target lesion) according to RECIST v1.1
- Stages 1 and 2: Adequate hematologic and end-organ function
- Stages 1 and 2: Stable anticoagulant regimen for patients receiving therapeutic anticoagulation
- ECOG Performance Status of 0 or 1
- Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection
- ER+, HER2-positive breast cancer
- +20 more criteria
You may not qualify if:
- Prior treatment with any of the protocol-specified study treatments
- Treatment with investigational therapy within 28 days prior to initiation of study treatment
- Systemic treatment for breast cancer within 2 weeks of Cycle 1, Day 1 or 5 half-lives of the drug prior to Cycle 1, Day 1
- Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug elimination half-lives (whichever is longer) prior to randomization
- Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤1 or better, with the exception of alopecia of any grade and Grade ≤2 peripheral neuropathy
- Eligible only for the control arm
- Prior allogeneic stem cell or solid organ transplantation
- Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
- History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
- Uncontrolled tumor-related pain
- Uncontrolled or symptomatic hypercalcemia
- Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
- History of leptomeningeal disease
- Active tuberculosis
- +71 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (31)
City of Hope
Duarte, California, 91010, United States
University of California, San Francisco (UCSF)
San Francisco, California, 94143, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Santa Monica, California, 90404, United States
Stanford Cancer Institute (SCI)
Stanford, California, 94305, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Regional Cancer Care Associates LLC (RCCA) - Freehold Location
Freehold, New Jersey, 07728, United States
Regional Cancer Care Associates LLC ? Howell Division
Howell Township, New Jersey, 07731, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, 15219, United States
West Cancer Center
Germantown, Tennessee, 38138, United States
Flinders Medical Centre
Bedford Park, South Australia, 5042, Australia
Peninsula Health-Frankston Hospital
Frankston, Victoria, 3199, Australia
Peter Maccallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Linear Clinical Research Limited
Nedlands, Western Australia, 6009, Australia
Shaare Zedek Medical Center
Jerusalem, Jerusalem, 9103102, Israel
Rambam Medical Center
Haifa, 3109601, Israel
Hadassah Ein Karem Hospital
Jerusalem, 91120, Israel
Rabin MC
Petah Tikva, 4941492, Israel
The Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Tel Aviv Sourasky Medical Center
Tel Aviv, 6423906, Israel
Assuta Medical Centers
Tel Aviv, 6971028, Israel
National Cancer Center
Goyang-si, 10408, South Korea
Samsung Medical Center
Seoul, (0)6351, South Korea
Seoul National University Hospital
Seoul, 03080, South Korea
Asan Medical Center
Seoul, 05505, South Korea
Severance Hospital
Seoul, 3722, South Korea
Hospital Universitario Vall d Hebron
Barcelona, 08035, Spain
Hospital Universitario Ramón y Cajal
Madrid, 28034, Spain
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
Madrid, 28050, Spain
Hospital Clinico Universitario de Valencia
Valencia, 46010, Spain
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Clinical Trials
Hoffmann-La Roche
Central Study Contacts
Reference Study ID Number: CO42867 https://forpatients.roche.com/
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 15, 2021
First Posted
March 17, 2021
Study Start
June 22, 2021
Primary Completion (Estimated)
May 30, 2029
Study Completion (Estimated)
May 30, 2029
Last Updated
April 13, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share
For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing