^
    7d
    Loss of luminal lineage drives resistance to next-generation ERα antagonists in pretreated ER+ HER2- locally-advanced or metastatic breast cancer. (PubMed, Nat Commun)
    In recent clinical trials of metastatic ER+ BC, next-generation SERDs demonstrated clinical activity, and elacestrant received an approval for advanced ESR1-mutant disease. NR tumors instead up-regulate multiple ERα-independent proliferative pathways, such as EGFR/MAPK and Hippo/TEAD, which may represent targetable dependencies in NR disease. Modeling resistance and lineage plasticity in vitro, we find that giredestrant-resistant ER+ BC cell lines exhibit profound shifts in chromatin accessibility, with the transcription factors, FOXA1 and FOXM1, implicated in gene expression of NR-upregulated proliferative pathways.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • FOXA1 (Forkhead Box A1) • FOXM1 (Forkhead Box M1)
    |
    ER positive • HER-2 negative • ESR1 mutation
    |
    Orserdu (elacestrant) • giredestrant (RG6171)
    26d
    ctDNA and tumor-based biomarkers of giredestrant response in acelERA breast cancer. (PubMed, Nat Commun)
    Furthermore, early ctDNA clearance identifies responding patients, and the combination of low ER activity and high ctDNA burden predicts rapid clinical progression. These findings provide a framework for personalizing future breast cancer therapies by integrating liquid biopsies with tissue-based signatures.
    Journal • Circulating tumor DNA
    |
    ER (Estrogen receptor)
    |
    ER positive • ESR1 mutation
    |
    giredestrant (RG6171)
    1m
    MiRaDoR: A PoC Study to Evaluate Treatments' Efficacy by Monitoring MRD Using ctDNA in HR-positive/HER2-negative EBC Population (clinicaltrials.gov)
    P2, N=976, Recruiting, MedSIR | Trial completion date: Dec 2028 --> Jun 2028 | Trial primary completion date: Dec 2028 --> Jun 2028
    Trial completion date • Trial primary completion date • Minimal residual disease • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • HR positive + HER-2 negative
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay • MammaPrint®
    |
    Verzenio (abemaciclib) • Itovebi (inavolisib) • giredestrant (RG6171)
    2ms
    A Study Evaluating the Efficacy and Safety of Adjuvant Giredestrant Compared With Physician's Choice of Adjuvant Endocrine Monotherapy in Participants With Estrogen Receptor-Positive, HER2-Negative Early Breast Cancer (lidERA Breast Cancer) (clinicaltrials.gov)
    P3, N=4170, Active, not recruiting, Hoffmann-La Roche | Trial primary completion date: Mar 2026 --> Aug 2025
    Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    tamoxifen • giredestrant (RG6171)
    2ms
    MedOPP485: A proof of concept study to evaluate treatmentsefficacy by monitoring Minimal Residual Disease using ctDNA in HR-positive/HER2-negative early breast cancer population (2023-505661-89-00`2022-002616-24)
    P1/2, N=1071, Recruiting, Medica Scientia Innovation Research S.L.
    New P1/2 trial • Minimal residual disease • Circulating tumor DNA
    |
    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HR positive • HER-2 negative • PIK3CA mutation • HR positive + HER-2 negative
    |
    therascreen® PIK3CA RGQ PCR Kit
    |
    Verzenio (abemaciclib) • Itovebi (inavolisib) • giredestrant (RG6171)
    2ms
    GO46021: To compare the Safety and activity of GDC-4198 Alone and in Combination with Giredestrant against Abemaciclib and Giredestrant in Participants with Breast Cancer (2025-521128-31-00)
    P1/2, N=73, Recruiting, Genentech Inc.
    New P1/2 trial
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    Verzenio (abemaciclib) • giredestrant (RG6171) • RG6794
    2ms
    A Study to Evaluate the Effect of GDC-4198 Alone and in Combination With Giredestrant Versus Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor Receptor-Negative (HER2-) Breast Cancer (clinicaltrials.gov)
    P1/2, N=285, Recruiting, Genentech, Inc. | Trial completion date: Jul 2030 --> Aug 2028 | Trial primary completion date: Jul 2030 --> Aug 2028
    Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    Verzenio (abemaciclib) • giredestrant (RG6171) • RG6794
    2ms
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (clinicaltrials.gov)
    P1, N=136, Recruiting, Genentech, Inc. | Trial completion date: Jul 2029 --> Apr 2030 | Trial primary completion date: Jul 2029 --> Apr 2030
    Trial completion date • Trial primary completion date • First-in-human
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    giredestrant (RG6171) • omeprazole
    2ms
    ZG005 combination hydrochloride gilteritinib tablets in patients with relapsed or refractory lymphoma: a multicentre, open-label, dose-exploration and dose-expansion phase I/II clinical study. (ChiCTR2500114728)
    P1/2, N=60, Recruiting, The First Affiliated Hospital of Zhejiang University School of Medicine; The First Affiliated Hospital of Zhejiang University School of Medicine
    New P1/2 trial
    |
    Xospata (gilteritinib) • giredestrant (RG6171) • nilvanstomig (ZG005) • ravoxertinib (RG7842)
    2ms
    Optimizing dose selection in oncology: the rationale for the clinical dose selection of giredestrant, an oral selective estrogen receptor degrader. (PubMed, Expert Opin Investig Drugs)
    Data were leveraged from preclinical and phase I/II studies in metastatic and early breast cancer, as a single agent and with palbociclib, to inform giredestrant dose selection. Our learnings challenge the MTD paradigm in drug development, particularly in targeted therapies, and demonstrate the importance of basing dose selection on the totality of evidence, including preclinical data, and may help inform the clinical development of future targeted therapies.
    Journal
    |
    ER (Estrogen receptor)
    |
    ER positive
    |
    Ibrance (palbociclib) • giredestrant (RG6171)
    3ms
    PREcoopERA: A Window-of-Opportunity Trial of Giredestrant +/- Triptorelin vs. Anastrozole + Triptorelin in Premenopausal Patients With ER-positive/HER2-negative Early Breast Cancer (clinicaltrials.gov)
    P2, N=231, Completed, ETOP IBCSG Partners Foundation | Recruiting --> Completed | Trial completion date: Jun 2026 --> Sep 2025 | Trial primary completion date: Jun 2026 --> Sep 2025
    Trial completion • Trial completion date • Trial primary completion date
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
    |
    ER positive • HER-2 negative
    |
    anastrozole • triptorelin • giredestrant (RG6171)
    3ms
    A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-0587 as a Monotherapy and in Combination With Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative (ER+/HER2-) Breast Cancer (clinicaltrials.gov)
    P1, N=136, Recruiting, Genentech, Inc. | Not yet recruiting --> Recruiting
    Enrollment open • First-in-human
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 negative
    |
    giredestrant (RG6171) • omeprazole