OncoMatch/Clinical Trials/NCT04802759
A Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Participants With Breast Cancer
Is NCT04802759 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments for inoperable, locally advanced or metastatic, er-positive breast cancer.
Treatment: Giredestrant · Abemaciclib · Ipatasertib · Inavolisib · Ribociclib · Everolimus · Samuraciclib · PH FDC SC · Palbociclib · Atezolizumab — 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.
Check if I qualifyExtracted eligibility criteria
Cancer type
Breast Carcinoma
Biomarker criteria
Required: ESR1 any mutation
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.
Required: PIK3CA any mutation
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.
Disease stage
Required: Stage III, IV
Metastatic disease required
locally advanced or metastatic disease not amenable to curative resection; Measurable disease (at least one target lesion) according to RECIST v1.1
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Must have received: endocrine therapy — locally advanced or metastatic
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.)
Cannot have received: cytotoxic chemotherapy
Exception: single agent capecitabine allowed (counts as a single line of therapy)
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)
Cannot have received: SERD (fulvestrant, novel oral SERD)
Exception: fulvestrant allowed if given more than 28 days prior to randomization (Cohort 2); prior fulvestrant therapy is allowed (Cohort 1)
Prior treatment with any SERD (e.g., fulvestrant, novel oral), proteolysis targeting chimera, complete ER antagonist (CERAN), or novel SERM (other than tamoxifen, toremifene)
Cannot have received: PI3K inhibitor
Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway
Cannot have received: AKT inhibitor
Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway
Cannot have received: mTOR inhibitor
Prior treatment with any PI3K, Akt, or mTOR inhibitor, or any agent whose mechanism of action is to inhibit the PI3K/Akt/mTOR pathway
Lab requirements
Blood counts
Adequate hematologic function
Kidney function
Adequate end-organ function
Liver function
Adequate end-organ function
Cardiac function
Baseline left ventricular ejection fraction (LVEF) ≥50% as measured by ECHO or MUGA scans (Cohort 2, Stages 1 and 2)
Adequate hematologic and end-organ function; Baseline left ventricular ejection fraction (LVEF) ≥50% as measured by ECHO or MUGA scans
Structured fields extracted by AI. May contain errors — verify against the official protocol.
US trial sites
- City of Hope · Duarte, California
- University of California, San Francisco (UCSF) · San Francisco, California
- Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center · Santa Monica, California
- Stanford Cancer Institute (SCI) · Stanford, California
- Massachusetts General Hospital · Boston, Massachusetts
Showing up to 5 US sites. See all sites on ClinicalTrials.gov →
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