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A clinical trial to compare the effectiveness and safety of giredestrant with a subcutaneous combination of pertuzumab and trastuzumab versus subcutaneous pertuzumab and trastuzumab alone in people with locally advanced or metastatic breast cancer, with HER2 and oestrogen receptor positivity
A Study to Evaluate the Efficacy and Safety of Giredestrant in Combination With Phesgo (Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf) Versus Phesgo in Participants With Locally Advanced or Metastatic Breast Cancer (heredERA Breast Cancer)
- Breast Cancer Er-Positive
- Breast Cancer HER-2 Positive
Trial Status:
Recruiting
This trial runs in
Countries
- Argentina
- China
- Germany
- Italy
- Mexico
- Portugal
- South Korea
- Spain
- Taiwan
- Thailand
- Turkey
- United States
Trial Identifier:
NCT05296798 2022-500014-26-00 WO43571
Trial Summary
This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction therapy with Phesgo plus taxane in participants with human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer (metastatic or locally advanced disease not amenable to curative treatment) who have not previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.
Hoffmann-La Roche
Sponsor
Phase 3
Phase
NCT05296798 , WO43571 , 2022-500014-26-00
Trial Identifier
All
Gender
≥18 Years
Age
No
Healthy Volunteers
Why is the heredERA clinical trial needed?
Breast cancer is a disease in which malignant (cancer) cells form in the breast tissue. Breast cancer can sometimes be diagnosed as “locally advanced unresectable” (the cancer has grown outside of the breast area, is not removable by surgery but has not yet spread to other parts of the body) or “metastatic” (the cancer has spread to other parts of the body). When breast cancer becomes locally advanced or metastatic, the effectiveness of current treatments could be improved.
The following characteristics can also play an important role in breast cancer:
- Human epidermal growth factor receptor (HER2)‒positive (sometimes this is written as “HER2+”): the cancer cells have HER2 receptors (proteins on the cell walls) in high amounts. Cancer cells that have high levels of HER2 are able to grow very quickly.
- Oestrogen receptor (ER)–positive (sometimes this is written as “ER+”): the cancer cells have receptors that allow them to use the hormone oestrogen to grow.
Researchers hope that using new drugs, like giredestrant, will provide better outcomes for people with HER2-positive and ER-positive breast cancer.
How does the heredERA clinical trial work?
This clinical trial is recruiting people who have locally advanced or metastatic HER2-positive, ER-positive breast cancer.
The purpose of this clinical trial is to compare the effects, good or bad, of giredestrant plus subcutaneous (under the skin) pertuzumab and trastuzumab (P + T) against subcutaneous P + T in people with locally advanced or metastatic HER2-positive, ER-positive breast cancer. Participants who take part in this clinical trial will receive either giredestrant plus subcutaneous P + T, or subcutaneous P + T.
All participants will also receive subcutaneous P + T and another approved chemotherapy drug, either docetaxel or paclitaxel, during the induction therapy phase. This is the regular treatment (sometimes called “standard of care”) for patients who are diagnosed with this type of cancer.
After the induction phase, if the participants’ cancer has not worsened and their heart function is preserved, they will enter the maintenance phase. During the maintenance phase, participants will be given the clinical trial treatment giredestrant plus subcutaneous P + T or subcutaneous P + T for as long as it can help them. Participants will be seen by the clinical trial doctor every 21 days. These hospital visits will include checks to see how the participant is responding to the treatment and any side effects they may be having. Participants’ total time in the clinical trial will depend on how their cancer responds to treatment. Participants are free to stop trial treatment and leave the clinical trial at any time.
What are the main endpoints of the heredERA clinical trial?
The main clinical trial endpoint (the main result that is measured in the trial to see if the medicine has worked) is how long participants live without their cancer worsening or dying due to any cause (progression-free survival).
The other clinical trial endpoints include the number and seriousness of any adverse events (unexpected medical problems that occur while on treatment), how long participants live (overall survival), and how many participants have a reduction in the size of their tumour (objective response rate).
Who can take part in this clinical trial?
People can take part in this trial if they are at least 18 years old and have been diagnosed with HER2-positive, ER-positive breast cancer that is either locally advanced or metastatic, and cannot be removed with surgery.
People may not be able to take part in this trial if they have certain other medical conditions, have previously received certain treatments, are pregnant or breastfeeding, or are planning to become pregnant.
What treatment will participants be given in this clinical trial?
This is an open-label trial, which means everyone involved, including the participants and the doctors, know which medicine is being used.
During the induction phase, all participants will receive P + T as a subcutaneous injection into the thigh every 21 days (each 21-day period is also called a “cycle”). They will also receive several cycles (normally 4–6, but no more than eight) of docetaxel or paclitaxel, each given as intravenous (into a vein) infusions.
During the maintenance phase, the participants will be split into two groups randomly (like flipping a coin) and given either:
- P + T, as a subcutaneous injection into the thigh every 21 days and giredestrant, as a capsule to be swallowed once every day
- OR P + T, as a subcutaneous injection into the thigh every 21 days.
Participants will have an equal chance of receiving either subcutaneous P + T plus giredestrant or subcutaneous P + T.
Are there any risks or benefits in taking part in this clinical trial?
The safety or effectiveness of the experimental treatment or use may not be fully known at the time of the trial. Most trials involve some risks to the participant, although it may not be greater than the risks related to routine medical care or the natural progression of the health condition. Potential participants will be told about any risks and benefits of taking part in the clinical trial, as well as any additional procedures, tests, or assessments they will be asked to undergo. These will all be described in an informed consent document (a document that provides people with the information they need to make a decision to volunteer for a clinical trial). A potential participant should also discuss these with members of the research team and with their usual healthcare provider. Anyone interested in taking part in a clinical trial should know as much as possible about the trial and feel comfortable asking the research team any questions about the trial.
Risks associated with the heredERA clinical trial
Participants may have side effects (an unwanted effect of a drug or medical treatment) from the drugs used in this clinical trial. Side effects can be mild to severe and even life-threatening, and can vary from person to person.
Giredestrant
Potential participants will be told about the known side effects of giredestrant, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
Giredestrant will be given as an oral capsule (to be swallowed). Participants will be told about any known side effects of oral administration.
P + T
Potential participants will be told about the known side effects of P + T, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
P + T will be given as a subcutaneous injection (under the skin, into the tissue layer between the skin and the muscle). Participants will be told about any known side effects of subcutaneous administration.
Docetaxel and paclitaxel
Potential participants will be told about the known side effects of docetaxel and paclitaxel, and where relevant, also potential side effects based on human and laboratory studies or knowledge of similar drugs.
Docetaxel and paclitaxel will each be given as an intravenous infusion (into a vein). Participants will be told about any known side effects of intravenous administration.
Potential benefits associated with the heredERA clinical trial
Participants' health may or may not improve from participation in the clinical trial, but the information that is collected may help other people who have a similar medical condition in the future.
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For more information about this clinical trial see the For Expert tab on the specific ForPatients page or follow these links to https://clinicaltrials.gov/ and/or https://euclinicaltrials.eu
Trial Summary
This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo after induction therapy with Phesgo plus taxane in participants with human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive advanced breast cancer (metastatic or locally advanced disease not amenable to curative treatment) who have not previously received a systemic non-hormonal anti-cancer therapy in the advanced setting.
Hoffmann-La Roche
Sponsor
Phase 3
Phase
NCT05296798 , WO43571 , 2022-500014-26-00
Trial Identifier
Phesgo, Giredestrant, Docetaxel, Paclitaxel, LHRH Agonist, Optional Endocrine Therapy of Investigator's Choice
Treatments
Locally Advanced or Metastatic Breast Cancer
Condition
Official Title
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
Eligibility Criteria
All
Gender
≥18 Years
Age
No
Healthy Volunteers
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 of induction therapy
- 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 trastuzumab, with or without pertuzumab, or ado-trastuzumab emtansine in the adjuvant setting
- 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
- 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
For the latest version of this information please go to www.forpatients.roche.com
