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Evaluating Giredestrant with Phesgo for Advanced Breast Cancer

A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Giredestrant in Combination With Phesgo Versus Phesgo After Induction Therapy With Phesgo + Taxane in Patients With Previously Untreated HER2-Positive, Estrogen Receptor-Positive Locally-Advanced or Metastatic Breast Cancer

Phase 3 Interventional Hoffmann-La Roche · NCT05296798

This study is testing if adding a new drug called giredestrant to Phesgo can help people with advanced HER2-positive, ER-positive breast cancer feel better compared to just using Phesgo alone.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment922 (estimated)
Ages18 Years and up
SexAll
SponsorHoffmann-La Roche Industry-sponsored
Drugs / interventionstrastuzumab, pertuzumab, lapatinib, neratinib, Doxorubicin
Locations237 sites (Tucson, Arizona and 236 other locations)
Trial IDNCT05296798 on ClinicalTrials.gov

What this trial studies

This Phase III, randomized, open-label study aims to assess the efficacy and safety of giredestrant in combination with Phesgo compared to Phesgo alone in patients with HER2-positive, ER-positive locally advanced or metastatic breast cancer. Participants must have measurable disease and have not received prior systemic non-hormonal therapy for their advanced condition. The study will involve multiple centers and will focus on patients who have had a disease-free interval of at least six months after previous treatments.

Who should consider this trial

Good fit: Ideal candidates include women with HER2-positive, ER-positive advanced breast cancer who have not received prior systemic non-hormonal therapy.

Not a fit: Patients with curable breast cancer or those who have previously received systemic non-hormonal therapy for advanced disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with advanced breast cancer who have limited treatment alternatives.

How similar studies have performed: Other studies have shown promising results with similar combinations of targeted therapies in advanced breast cancer, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Histologically or cytologically confirmed and documented human epidermal growth factor receptor 2 (HER2)-positive/estrogen receptor (ER)-positive adenocarcinoma of the breast with metastatic or locally-advanced disease not amenable to curative resection
* At least one measurable lesion and/or non-measurable disease evaluable according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
* Disease-free interval from completion of adjuvant or neoadjuvant systemic non-hormonal treatment to recurrence of ≥6 months
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1
* Left ventricular ejection fraction (LVEF) of at least (≥)50% measured by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA)
* Adequate hematologic and end-organ function
* For women of childbearing potential: Participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agree to refrain from donating eggs, during the treatment period and for 7 months after the final dose of Phesgo
* For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, during the treatment period and for 7 months after the final dose of Phesgo to avoid exposing the embryo

Maintenance Phase Inclusion Criteria

* Complete a minimum of four cycles to a maximum of eight cycles of induction therapy; the minimum cycles are defined as either: Phesgo injections + 4 docetaxel infusions, or Phesgo injections + 12 paclitaxel infusions
* Achieve a minimum of stable disease (SD) (or Non-complete response \[CR\]/Non-progressive disease \[PD\] for participants with non-measurable disease) (i.e., did not experience PD) according to RECIST v1.1 at the last tumor assessment during the induction therapy phase
* LVEF of ≥50% at the last assessment during the induction therapy phase

Exclusion Criteria:

* Previous systemic non-hormonal anti-cancer therapy in the metastatic breast cancer (MBC) or advanced breast cancer (ABC) setting. Note: Up to one line of single-agent endocrine therapy given in the metastatic or locally advanced setting will be allowed.
* Prior treatment with a selective estrogen receptor degrader (SERD)
* Previous treatment with approved or investigative anti-HER2 agents in any breast cancer treatment setting, except Phesgo (or trastuzumab SC with pertuzumab IV, or pertuzumab and trastuzumab IV), single-agent trastuzumab IV or SC, ado-trastuzumab emtansine, lapatinib, and neratinib in the neoadjuvant or adjuvant setting
* Disease progression within 6 months of receiving adjuvant anti-HER2 therapy (such as trastuzumab, with or without pertuzumab \[IV, SC, or fixed-dose combination\], or ado-trastuzumab emtansine, or neratinib)
* Non-resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0) Grade 1 or better
* History of persistent Grade ≥2 (NCI-CTC, Version 5.0) hematological toxicity resulting from previous adjuvant or neo-adjuvant therapy
* History of exposure to the following cumulative doses of anthracyclines; Doxorubicin \>360 mg/m2; Liposomal doxorubicin \>500 mg/m2; Epirubucin \>720 mg/m2; Mitoxantrone \>120 mg/m2; Idarubicin \>90 mg/m2.
* Known active uncontrolled or symptomatic central nervous system (CNS) metastases, carcinomatous meningitis, or leptomeningeal disease
* Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy
* Pregnant or breastfeeding, or intending to become pregnant during the study or within 7 months after the final dose of Phesgo (Women of childbearing potential must have a negative serum pregnancy test result within 14 days prior to initiation of induction therapy).
* Treated with investigational therapy within 28 days prior to initiation of induction therapy
* Treated with localized palliative radiotherapy within 14 days prior to initiation of induction therapy
* Concurrent participation in any other therapeutic clinical trial
* Known hypersensitivity to any of the study medications or to excipients of recombinant human or humanized antibodies
* Current chronic daily treatment (continuous for \>3 months) with corticosteroids (dose of 10 mg/day methylprednisolone or equivalent)
* Poorly controlled hypertension
* Known clinically significant history of liver disease consistent with Child-Pugh Class B or C, active liver disease including active viral or other hepatitis virus, autoimmune hepatic disorders, or sclerosing cholangitis, current alcohol abuse, or cirrhosis
* Active cardiac disease or history of cardiac dysfunction
* Major surgical procedure or significant traumatic injury within 14 days prior to enrollment or anticipation of need for major surgery during induction therapy
* Active inflammatory bowel disease, chronic diarrhea, short bowel syndrome, or major upper gastrointestinal surgery
* Concurrent, serious, uncontrolled infections, or known infection with HIV with the following exception: Individuals who are HIV positive are eligible provided they are stable on anti-retroviral therapy for ≥4 weeks, have a CD4 count ≥350 cells/uL, and have an undetectable viral load and no history of AIDS-defining opportunistic infections within 12 months prior to enrollment.
* Serious COVID-19 infection within 14 days prior to enrollment; however, no screening testing for SARS-CoV-2 is required
* Serious infection requiring oral or IV antibiotics within 7 days prior to screening
* Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in the study
* History of malignancy within 5 years prior to screening with the exception of the cancer under investigation in this study and malignancies with a negligible risk of metastasis or death
* For pre- and perimenopausal women, and men: Known hypersensitivity to luteinizing hormone-releasing hormone agonist (LHRHa); Not willing to undergo and maintain treatment with approved LHRHa therapy for the duration of endocrine therapy that requires gonadal function suppression
* Treatment with strong CYP3A4 inhibitors or inducers within 14 days or 5 drug-elimination half-lives, whichever is longer, prior to initiation of giredestrant treatment in Arm B
* A documented history of hemorrhagic diathesis, coagulopathy, or thromboembolism, including deep vein thrombosis, unless the condition is adequately treated and under control

Where this trial is running

Tucson, Arizona and 236 other locations

+187 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Locally Advanced or Metastatic Breast Cancer
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.