Study of Multiple Treatment Combinations for ER-positive Breast Cancer
This study is evaluating different combinations of medications for women with advanced or metastatic estrogen receptor-positive (ER+) breast cancer that has progressed after prior treatment. The medications being tested include giredestrant, abemaciclib, ipatasertib, inavolisib, and ribociclib. Researchers want to see how effective these combinations are at shrinking tumors (objective response) and if they are safe, by tracking side effects (adverse events). You may be eligible if you are an adult woman with ER-positive, HER2-negative breast cancer that is inoperable, locally advanced, or metastatic, and has progressed after a CDK4/6 inhibitor (like palbociclib, ribociclib, or abemaciclib).
- Study design
- This is a Phase Ib/II, open-label, multi-center, randomized umbrella study with 316 planned participants. It is designed to be flexible, allowing new treatments to be added or removed.
- What's involved
- Not specified in the trial record.
- Compensation
- Not stated in the trial record.
- Follow-up
- Participants will be followed for objective response until disease progression (up to 6 years) and for adverse events until 30 days after the last dose of study drug (up to 6 years).
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT04802759
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
Recruiting
PHASE1Ages 18+InterventionalTreatmentHoffmann-La Roche
~316 participants
Updated 2026-08-05 on ClinicalTrials.gov
What's tested:GiredestrantAbemaciclibIpatasertibInavolisibRibociclibEverolimus
At a glance
Recruiting sites
29 of 32 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
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 over From Baseline until disease progression (up to 6 years)
+1 more outcome measured
Conditions
Where it's being run
32 sites across 13 statesIsrael6
California5
South Korea5
Spain4
New Jersey2
Pennsylvania2
Victoria2
Massachusetts1
Study leadership
- Clinical Trials · STUDY_DIRECTOR · Hoffmann-La Roche
Who to contact
Reference Study ID Number: CO42867 https://forpatients.roche.com/ No attachments to email below.
Opens a ready-to-send draft in your own email app — review before sending.
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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
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.
Exclusion
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
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
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
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
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.
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
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
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
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
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
What this trial measures
- 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)