AzTrials
AzTrials

Inoperable, Locally Advanced or Metastatic, ER-positive Breast CancerPhase 1/2NCT04802759

A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer

A Phase 1/2 study testing Giredestrant, Abemaciclib and Ipatasertib in people with Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer, run by Hoffmann-La Roche at 32 sites in 5 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Giredestrant, Abemaciclib and Ipatasertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
316 participants
Where
32 sitesin 5 countries
Study dates
22 Jun 2021to 30 May 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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

  • Inclusion Criteria for Cohort 1 (Stage 1 [and Stage 2, only where indicated]):
  • 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.)
Show all 37Show fewer
  • 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
  • Inclusion Criteria for Cohort 2 (Stage 1 [and Stage 2, only where indicated]):
  • 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
  • Postmenopausal status for women
  • Life expectancy ≥3 months
  • Willingness to have a representative tumor specimen that is suitable for biomarker evaluation via central testing submitted, if available
  • Prior endocrine therapy in the advanced setting allowed, including fulvestrant if given more than 28 days prior to randomization, but excluding other selective estrogen receptor degraders (SERDs)
  • Stages 1 and 2: Measurable disease (at least one target lesion) according to RECIST v1.1
  • Stages 1 and 2: Baseline left ventricular ejection fraction (LVEF) ≥50% as measured by ECHO or MUGA scans
  • Stages 1 and 2: Adequate hematologic and end-organ function
  • Stages 1 and 2: Stable anticoagulant regimen for patients receiving therapeutic anticoagulation
  • Ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, disease progression as determined by the investigator according to RECIST v1.1, or loss of clinical benefit as determined by the investigator, provided that a Stage 2 slot is available and patient meets eligibility criteria for Stage 2
  • Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 because of unacceptable toxicity to drugs, disease progression as determined by the investigator according to RECIST v1.1, or loss of clinical benefit as determined by the investigator
  • Measurable disease (at least one target lesion) according to RECIST v1.1
  • ECOG Performance Status of 0 or 1
  • Documented 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
  • Histologically or cytologically confirmed and documented adenocarcinoma of the breast that is locally advanced or metastatic and is not amenable to surgical or radiation therapy with curative intent
  • Patients must have progressed during adjuvant endocrine treatment or within 12 months of completing adjuvant endocrine therapy with an aromatase inhibitor or tamoxifen. If a CDK4/6i was included as part of neoadjuvant or adjuvant therapy, progression event must be >12 months since completion of CDK4/6i portion of neoadjuvant or adjuvant therapy.
  • Postmenopausal status for women (including women on or starting luteinizing hormone-releasing hormone [LHRH] agonist for ovarian suppression prior to randomization)
  • Life expectancy ≥6 months
  • Adequate hematologic and end-organ function
  • Evidence of an eligible PIK3CA mutation based on pre-existing test results (i.e., previously obtained as part of clinical practice) from blood or tumor tissue. If pre-existing test results are not available, submission of a freshly collected pretreatment blood sample to determine PIK3CA mutation status at a central testing site with the FoundationOne Liquid® CDx assay is required.

Who cannot join

  • General Exclusion Criteria for all Treatment Arms in Stage 1, Cohorts 1 and 2 (unless only applicable to one cohort, as indicated):
  • 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
Show all 95Show fewer
  • 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
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
  • Active cardiac disease or history of cardiac dysfunction
  • Positive HIV test at screening or at any time prior to screening
  • Active Hepatitis B or Hepatitis C virus infection
  • Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery, including gastric resection, potentially affecting enteral absorption
  • Known allergy or hypersensitivity to any of the study drugs or any of their excipients
  • Cohort 1 only: Known HER2-positive breast cancer
  • Cohort 1 only: Concurrent hormone replacement therapy
  • Cohort 1 only: Prior treatment with cytotoxic chemotherapy for metastatic breast cancer (with the exception of single agent capecitabine, which will count as a single line of therapy)
  • Cohort 2 only: Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
  • Cohort 2 only: Current chronic daily treatment (continuous for >3 months) with corticosteroids (dose of 10 mg/day methylprednisolone equivalent), excluding inhaled steroids
  • Additional Exclusion Criteria for Giredestrant + Abemaciclib Arm and Giredestrant + Abemaciclib + Atezolizumab Arm (Cohort 1, Stage 1):
  • Interstitial lung disease or severe dyspnea at rest or requiring oxygen therapy
  • History of major surgical resection involving the stomach or small bowel, or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea
  • History of syncope of cardiovascular etiology, ventricular arrhythmia, or sudden cardiac arrest
  • Additional Exclusion Criteria for Giredestrant + Ipatasertib Arm (Cohort 1, Stage 1):
  • Prior treatment with an Akt inhibitor
  • Inability to swallow medication or malabsorption condition that would alter the absorption of orally administered medications
  • Grade ≥2 uncontrolled or untreated hypercholesterolemia or hypertriglyceremia
  • History of Type 1 or Type 2 diabetes mellitus requiring insulin
  • History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion
  • Additional Exclusion Criteria for the Giredestrant + Inavolisib and Giredestrant + Inavolisib (ESR1m enriched) Arms (Cohort 1, Stage 1):
  • Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway
  • Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
  • Fasting glucose ≥126 mg/dL or ≥7.0 mmol/L and HbA1c ≥5.7% (or HbA1c ≥6.4% for the ESR1m enriched Arm only)
  • Any concurrent ocular or intraocular condition, excluding baseline cataracts, that, in the opinion of the investigator, would require medical or surgical intervention during the study period to prevent or treat vision loss
  • Active inflammatory or infectious conditions in either eye or history of idiopathic or autoimmune-associated uveitis in either eye
  • Symptomatic active lung disease, including pneumonitis
  • Inability to confirm biomarker eligibility based on valid results from either central testing of blood or local testing of blood or tumor tissue that documents one of the protocol-defined PIK3CA mutations
  • ESR1m enriched Arm only: Inability to determine ESR1 mutation status based on valid results from either central testing of blood or from pre-existing test results (from blood or tumor tissue) that confirm the presence of an ESR1 mutation. While patients who have tumors without detectable ESR1 mutation may be enrolled in this arm, a pre-existing test with no detectable ESR1m result is not acceptable for enrollment, and the participant in this case must submit a sample for central testing.
  • Additional Exclusion Criteria for Giredestrant + Ribociclib Arm (Cohort 1, Stage 1):
  • Currently receiving or has received systemic corticosteroids ≤2 weeks prior to starting trial treatment
  • Impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
  • Additional Exclusion Criteria for Giredestrant + Samuraciclib Arm (Cohort 1, Stage 1):
  • Prior treatment with mTOR inhibitor
  • Receipt of systemic corticosteroids (at a dose >10 mg prednisone/day or equivalent) within 14 days before the first dose of samuraciclib
  • Active bleeding diatheses
  • History of hemolytic anemia or marrow aplasia
  • Receipt of a live-virus vaccination within 28 days or less of planned treatment start
  • Additional Exclusion Criteria for Giredestrant + Atezolizumab-Containing Arms (Cohort 1, Stage 1):
  • Active or history of autoimmune disease or immune deficiency
  • Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
  • Treatment with systemic immunostimulatory agents within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
  • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
  • Known hypersensitivity to Chinese hamster ovary cell products or recombinant human antibodies
  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
  • Pregnant or breastfeeding, or intending to become pregnant during study treatment or within 5 months for atezolizumab
  • Additional Exclusion Criteria for Giredestrant + PH FDC SC + Abemaciclib Arm (Cohort 2, Stage 1):
  • Interstitial lung disease or severe dyspnea
  • History of major surgical resection involving the stomach or small bowel, preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea, or a condition that may significantly alter the absorption of the oral trial treatments
  • History of syncope of cardiovascular etiology, ventricular arrhythmia, or sudden cardiac arrest
  • Additional Exclusion Criteria for Giredestrant + PH FDC SC + Palbociclib Arm (Cohort 2, Stage 1):
  • History of major surgical resection involving the stomach or small bowel, preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea, or a condition that may significantly alter the absorption of the oral trial treatments
  • Interstitial lung disease or severe dyspnea
  • Known HER2-positive breast cancer
  • Prior treatment with any SERD (e.g., fulvestrant, novel oral), proteolysis targeting chimera, complete ER antagonist (CERAN), or novel SERM (other than tamoxifen, toremifene)
  • Prior treatment with any PI3Kalpha (PIK3CA gene product), AKT or mTOR inhibitor
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • 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
  • Major surgical procedure 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
  • Severe infection within 4 weeks prior to initiation of study treatment
  • Treatment for clinically significant infection with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
  • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
  • Active cardiac disease or history of cardiac dysfunction
  • Positive HIV test at screening or at any time prior to screening
  • Active Hepatitis B or Hepatitis C virus infection
  • Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal (GI) surgery, including gastric resection, potentially affecting enteral absorption
  • Known allergy or hypersensitivity to any of the study drugs or any of their excipients

Trial locations and contacts

32 sites in 5 countries. Contact the study team or a site near you to ask about taking part.

Reference Study ID Number: CO42867 https://forpatients.roche.com/ No attachments to email below. contact

888-662-6728 (U.S. Only)

global-roche-genentech-trials@gene.com

Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact

32 sites in 5 countries

United States12 sites, 9 recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

    Recruiting

  • Levine Cancer Institute

    Charlotte, North Carolina, 28204

    Recruiting

  • City of Hope

    Duarte, California, 91010

    Recruiting

  • Regional Cancer Care Associates LLC (RCCA) - Freehold Location

    Freehold, New Jersey, 07728

    Withdrawn

  • West Cancer Center

    Germantown, Tennessee, 38138

    Recruiting

  • Regional Cancer Care Associates LLC ? Howell Division

    Howell Township, New Jersey, 07731

    Withdrawn

  • City of Hope - Orange County Lennar Foundation Cancer Center

    Irvine, California, 92618-2377

    Recruiting

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

    Recruiting

  • University of Pittsburgh Cancer Institute

    Pittsburgh, Pennsylvania, 15219

    Withdrawn

  • University of California, San Francisco (UCSF)

    San Francisco, California, 94143

    Recruiting

  • Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

    Santa Monica, California, 90404

    Recruiting

  • Stanford Cancer Institute (SCI)

    Stanford, California, 94305

    Recruiting

Other trials in United States

Israel7 sites, 7 recruiting

  • Rambam Medical Center

    Haifa, 3109601

    Recruiting

  • Shaare Zedek Medical Center

    Jerusalem, Jerusalem, 9103102

    Recruiting

  • Hadassah Ein Karem Hospital

    Jerusalem, 91120

    Recruiting

  • Rabin MC

    Petah Tikva, 4941492

    Recruiting

  • The Chaim Sheba Medical Center

    Ramat Gan, 52621

    Recruiting

  • Tel Aviv Sourasky Medical Center

    Tel Aviv, 6423906

    Recruiting

  • Assuta Medical Centers

    Tel Aviv, 6971028

    Recruiting

Other trials in Israel

South Korea5 sites, 5 recruiting

  • National Cancer Center

    Goyang-si, 10408

    Recruiting

  • Samsung Medical Center

    Seoul, (0)6351

    Recruiting

  • Seoul National University Hospital

    Seoul, 03080

    Recruiting

  • Asan Medical Center

    Seoul, 05505

    Recruiting

  • Severance Hospital

    Seoul, 3722

    Recruiting

Other trials in South Korea

Australia4 sites, 4 recruiting

  • Flinders Medical Centre

    Bedford Park, South Australia, 5042

    Recruiting

  • Peninsula Health-Frankston Hospital

    Frankston, Victoria, 3199

    Recruiting

  • Peter Maccallum Cancer Centre

    Melbourne, Victoria, 3000

    Recruiting

  • Linear Clinical Research Limited

    Nedlands, Western Australia, 6009

    Recruiting

Other trials in Australia

Spain4 sites, 4 recruiting

  • Hospital Universitario Vall d Hebron

    Barcelona, 08035

    Recruiting

  • Hospital Universitario Ramón y Cajal

    Madrid, 28034

    Recruiting

  • Centro Integral Oncológico Clara Campal Ensayos Clínicos START

    Madrid, 28050

    Recruiting

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

    Recruiting

Other trials in Spain

About this study

Official title: 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)

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.

Read more

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.

Being tested
Giredestrant, Abemaciclib, Ipatasertib, Inavolisib, Ribociclib
Medical subject headings
Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GiredestrantDrug

    Also called GDC-9545, RO7197597, RG6171

    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

  • AbemaciclibDrug

    Also called Verzenio™

    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

  • IpatasertibDrug

    Also called GDC-0068, RO5532961, RG7440

    400 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

  • InavolisibDrug

    Also called ITOVEBI™, GDC-0077, RO7113755, RG6114

    9 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

  • RibociclibDrug

    Also called Kisqali®

    600 mg orally once a day on Days 1-21 of each 28-day cycle until unacceptable toxicity or disease progression

  • EverolimusDrug

    Also called Afinitor®

    10 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

  • SamuraciclibDrug

    Also called ICEC0942, CT7001

    360 mg orally once a day during each 28-day cycle until unacceptable toxicity or disease progression

  • PH FDC SCDrug

    Also called Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO™, RO7198574, RG6264

    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.

  • PalbociclibDrug

    Also called Ibrance®

    125 mg orally once a day on Days 1-21 during each 28-day cycle until unacceptable toxicity or disease progression

  • AtezolizumabDrug

    Also called Tecentriq®, RO5541267, RG7446

    840 mg by intravenous (IV) infusion on Days 1 and 15 each 28-day cycle.

Study groups in NCT04802759
Study groupRoleWhat they receive
Cohort 1: Giredestrant MonotherapyActive comparatorNot described
Receives: Drug: Giredestrant
Cohort 1: Giredestrant + AbemaciclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Abemaciclib
Cohort 1: Giredestrant + IpatasertibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Ipatasertib
Cohort 1: Giredestrant + InavolisibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Inavolisib
Cohort 1: Giredestrant + RibociclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Ribociclib
Cohort 1: Giredestrant + EverolimusExperimentalNot described
Receives: Drug: Giredestrant; Drug: Everolimus
Cohort 1: Giredestrant + SamuraciclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Samuraciclib
Cohort 1: Giredestrant + AtezolizumabExperimentalNot described
Receives: Drug: Giredestrant; Drug: Atezolizumab
Cohort 1: Giredestrant + Abemaciclib + AtezolizumabExperimentalNot described
Receives: Drug: Giredestrant; Drug: Abemaciclib; Drug: Atezolizumab
Cohort 1: Giredestrant + Inavolisib (ESR1m enriched)ExperimentalESR1m stands for estrogen receptor mutation.
Receives: Drug: Giredestrant; Drug: Inavolisib
Cohort 2: Giredestrant + PH FDC SCActive comparatorNot described
Receives: Drug: Giredestrant; Drug: PH FDC SC
Cohort 2: Giredestrant + PH FDC SC + AbemaciclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Abemaciclib; Drug: PH FDC SC
Cohort 2: Giredestrant + PH FDC SC + PalbociclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: PH FDC SC; Drug: Palbociclib
Cohort 3: Giredestrant + Inavolisib + PalbociclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Inavolisib; Drug: Palbociclib
Cohort 3: Giredestrant + Inavolisib + AbemaciclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Abemaciclib; Drug: Inavolisib
Cohort 3: Giredestrant + Inavolisib + RibociclibExperimentalNot described
Receives: Drug: Giredestrant; Drug: Inavolisib; Drug: Ribociclib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

    Measured: From Baseline until disease progression (up to 6 years)

  2. 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)

    Measured: From Baseline until 30 days after the last dose of study drug (up to 6 years)

Secondary outcomes (5)

  1. Progression-Free Survival, as Determined by the Investigator According to RECIST v1.1

    Measured: 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)

  2. 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

    Measured: From Baseline until disease progression (up to 6 years)

  3. 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

    Measured: From Baseline until disease progression (up to 6 years)

  4. Overall Survival

    Measured: From randomization to death from any cause (up to 6 years)

  5. Duration of Response, as Determined by the Investigator According to RECIST v1.1

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Mar 2021
  2. Study start22 Jun 2021
  3. Primary completion30 May 2029 (estimated)
  4. Study completion30 May 2029 (estimated)

Resources

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
Parallel groups
Masking
None (open label)
Enrolment
316 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04802759
Sponsor's protocol ID
CO42867
Other IDs
2020-004889-19, 2023-507495-48-00, 2023
Status last verified
Oct 2026
First submitted
15 Mar 2021
Last updated
6 Oct 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Giredestrant, Abemaciclib and Ipatasertib in people with Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer, run by Hoffmann-La Roche at 32 sites in 5 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 37 inclusion and 95 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: looking for participants now, as of the sponsor's last update on 6 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States, Israel, South Korea, Australia, Spain. 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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Reference Study ID Number: CO42867 https://forpatients.roche.com/ No attachments to email below. (888-662-6728 (U.S. Only), global-roche-genentech-trials@gene.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: From Baseline until disease progression (up to 6 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04802759.

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 6 Oct 2026.

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