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

Recruiting now · Phase 1/Phase 2

Conditions studied: Inoperable, Locally Advanced or Metastatic, ER-positive Breast Cancer

In brief

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.

Key facts

Study ID

NCT04802759

Run by

Hoffmann-La Roche

People needed

316

Starts

2021-06-22

Expected to finish

2029-05-30

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• 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.)
• 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

You may not qualify if…

• 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
• 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

Where it is running

• Hospital Clinico Universitario de Valencia — Valencia, Spain (enrolling)
• City of Hope - Orange County Lennar Foundation Cancer Center — Irvine, California, United States (enrolling)
• University of California, San Francisco (UCSF) — San Francisco, California, United States (enrolling)
• Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center — Santa Monica, California, United States (enrolling)
• Stanford Cancer Institute (SCI) — Stanford, California, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• Hospital Universitario Ramón y Cajal — Madrid, Spain (enrolling)
• Centro Integral Oncológico Clara Campal Ensayos Clínicos START — Madrid, Spain (enrolling)
• City of Hope — Duarte, California, United States (enrolling)
• Levine Cancer Institute — Charlotte, North Carolina, United States (enrolling)
• Thomas Jefferson University Hospital — Philadelphia, Pennsylvania, United States (enrolling)
• West Cancer Center — Germantown, Tennessee, United States (enrolling)
• Flinders Medical Centre — Bedford Park, South Australia, Australia (enrolling)
• Peninsula Health-Frankston Hospital — Frankston, Victoria, Australia (enrolling)
• Peter Maccallum Cancer Centre — Melbourne, Victoria, Australia (enrolling)
• Linear Clinical Research Limited — Nedlands, Western Australia, Australia (enrolling)
• Shaare Zedek Medical Center — Jerusalem, Jerusalem, Israel (enrolling)
• Rambam Medical Center — Haifa, Israel (enrolling)
• Hadassah Ein Karem Hospital — Jerusalem, Israel (enrolling)
• Rabin MC — Petah Tikva, Israel (enrolling)
• The Chaim Sheba Medical Center — Ramat Gan, Israel (enrolling)
• Tel Aviv Sourasky Medical Center — Tel Aviv, Israel (enrolling)
• Assuta Medical Centers — Tel Aviv, Israel (enrolling)
• National Cancer Center — Goyang-si, South Korea (enrolling)
• Samsung Medical Center — Seoul, South Korea (enrolling)

Full record on ClinicalTrials.gov

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