Giredestrant + Hormone Therapy for Early-Stage Breast Cancer

Not currently recruiting at 1041 trial locations

Overseen By Reference Study ID Number: GO42784 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must not be taking: CDK4/6 inhibitors, CYP3A4 inhibitors

Disqualifiers: Stage IV breast cancer, Cardiac disease, Liver disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment option for individuals with certain types of early-stage breast cancer. The primary goal is to compare the effects of giredestrant, a new hormone therapy, with standard hormone therapies typically chosen by doctors. It includes participants with estrogen receptor-positive breast cancer (cancer that grows in response to estrogen) and HER2-negative breast cancer (lacking a protein that promotes cancer growth), who have already undergone surgery and possibly chemotherapy. An additional part of the trial will test giredestrant combined with another drug, abemaciclib, in some participants. This combination may suit those who have had surgery for breast cancer and have not yet started hormone therapy. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial requires a washout period (time without taking certain medications) of at least 21 days after the last dose of adjuvant chemotherapy before starting the study. Additionally, you cannot take strong CYP3A4 inhibitors or inducers within 14 days before starting the study treatment. If you are on these medications, you may need to stop them before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that giredestrant is generally safe for people. One study found its safety profile similar to other hormone treatments that lower estrogen levels, with expected side effects. These side effects are typical for this kind of treatment, suggesting it is usually safe to use.

Early results indicate that the combination of giredestrant and abemaciclib is also generally safe. In trials with patients who had previous treatments, this combination was well tolerated. While side effects may occur, they are manageable and expected for this type of treatment.

In summary, both giredestrant alone and with abemaciclib have demonstrated general safety in past studies. Those considering joining this trial can be assured that these treatments have been tested for safety in similar situations before. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about giredestrant for early-stage breast cancer because it offers a novel approach to hormone therapy. Unlike traditional endocrine therapies like tamoxifen or aromatase inhibitors, giredestrant is a selective estrogen receptor degrader (SERD), which means it not only blocks estrogen receptors but also degrades them, potentially leading to more effective tumor suppression. Additionally, in one arm of the study, giredestrant is combined with abemaciclib, a CDK4/6 inhibitor, which further enhances its ability to halt cancer cell growth by interfering with the cell cycle. This combination could provide a more robust and targeted treatment option compared to existing therapies.

What evidence suggests that this trial's treatments could be effective for early-stage breast cancer?

Research has shown that giredestrant may effectively treat estrogen receptor-positive, HER2-negative breast cancer. In this trial, one group of participants will receive giredestrant alone, while another will receive endocrine therapy chosen by the physician. Additionally, a substudy will evaluate the combination of giredestrant with abemaciclib for up to 2 years, followed by giredestrant monotherapy for an additional 3 years. Studies have found that giredestrant, especially when combined with everolimus, can reduce the risk of cancer progression or death by up to 62% in some individuals. Giredestrant alone has slowed tumor growth more effectively than tamoxifen, a common treatment for early-stage breast cancer. Furthermore, using giredestrant with abemaciclib, a drug that inhibits cancer cell division, has proven effective in similar cases, helping to prevent cancer recurrence. These findings suggest that giredestrant, whether used alone or with other drugs, could be a strong option for managing early-stage breast cancer. ^{1 2 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

This trial is for adults with early-stage, estrogen receptor-positive, HER2-negative breast cancer who've had surgery and possibly chemotherapy (with a 21-day gap before joining the study). They should be within 12 months post-surgery, have no prior endocrine therapy or other cancers in the last 3 years, and must not be pregnant. Good organ function and performance status are required.

Inclusion Criteria

My breast cancer is estrogen receptor positive and HER2 negative.

I finished my additional chemotherapy at least 3 weeks ago.

All my breast cancer tumors are ER positive and HER2 negative.

Exclusion Criteria

Received treatment with investigational therapy within 28 days prior to initiation of study treatment or is currently enrolled in any other type of medical research judged by the sponsor not to be scientifically or medically compatible with this study

I am taking or will take a CDK4/6 inhibitor for early-stage cancer treatment.

I have severe liver disease, such as hepatitis or cirrhosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive adjuvant giredestrant or endocrine therapy of physician's choice

5 years

Substudy Treatment

Participants in the substudy receive giredestrant in combination with abemaciclib for up to 2 years, followed by giredestrant monotherapy for an additional 3 years

5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Endocrine Therapy of Physician's Choice
• Giredestrant
• LHRH Agonist

Trial Overview The study compares Giredestrant, a new drug for breast cancer treatment after surgery (adjuvant), to standard endocrine therapies chosen by physicians. It's an open-label Phase III trial where participants are randomly assigned to either treatment group.

How Is the Trial Designed?

Group I: Substudy: Giredestrant + Abemaciclib, Then Giredestrant Experimental Treatment 2 Interventions

In this substudy, participants will receive giredestrant in combination with abemaciclib for up to 2 years. Participants will continue with giredestrant monotherapy for an additional 3 years in order to complete a total of 5 years on study treatment.

Group II: Arm A: Giredestrant Experimental Treatment 2 Interventions

Group III: Arm B: Endocrine Therapy of Physician's Choice Active Control 2 Interventions

Endocrine Therapy of Physician's Choice is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in United States as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Canada as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Japan as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in China as Endocrine Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Switzerland as Hormone Therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Published Research Related to This Trial

Aromatase inhibitors (AIs) provide a significant survival benefit for postmenopausal women with advanced breast cancer compared to other endocrine therapies, with a pooled hazard ratio of 0.90 based on 31 trials involving 11,403 women.

AIs have a different toxicity profile than other endocrine treatments, showing similar rates of hot flushes and arthralgia, but significantly lower risks of vaginal bleeding (71% decrease) and thromboembolic events (47% decrease).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors for treatment of advanced breast cancer in postmenopausal women. Gibson, L., Lawrence, D., Dawson, C., et al.[2022]

Endocrine therapy, particularly with tamoxifen, has improved safety and rationale in treating breast cancer, but uncertainties remain regarding its effectiveness compared to chemotherapy, especially in adjuvant settings.

In advanced breast cancer, a sequential approach using either endocrine therapy or chemotherapy is preferred over concurrent treatment, although specific clinical situations may warrant the latter approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results and limits of endocrine therapy of carcinoma of the breast]. Cocconi, G.[2006]

Endocrine therapy, particularly with tamoxifen, is a key treatment for women with steroid receptor-positive breast cancers, significantly lowering the risk of recurrence and death.

For premenopausal women, ovarian suppression is a crucial option, while postmenopausal women may benefit from aromatase inhibitors, highlighting the need for ongoing research into the best treatment sequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Adjuvant treatment of breast cancer. Endocrine therapy]. Mouridsen, HT., Andersen, J.[2013]

Anti-aromatase agents, such as exemestane and anastrozole, have shown better tolerability and improved efficacy compared to megestrol acetate for postmenopausal women with advanced breast cancer who have progressed after tamoxifen therapy.

These agents are now considered the preferred endocrine treatment option due to their demonstrated survival benefits and effectiveness in patients who have failed multiple hormonal therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anti-aromatase agents in postmenopausal advanced breast cancer. Murray, R.[2019]

Endocrine therapy is crucial for treating breast cancer but can lead to cognitive dysfunction, which is common and often underreported, affecting patients' quality of life and treatment adherence.

A comprehensive literature review highlights the need for proactive management of cognitive side effects associated with endocrine therapies, emphasizing the importance of a multi-disciplinary approach to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Endocrine Therapy on Cognitive Function in Patients with Breast Cancer: A Comprehensive Review. Haggstrom, LR., Vardy, JL., Carson, EK., et al.[2022]

Endocrine therapy, particularly targeting estrogen receptors (ER), is crucial for treating both primary and advanced breast cancer, with ER status being the best predictor of treatment response.

New agents, such as pure anti-estrogens and third-generation selective aromatase inhibitors, are emerging as effective alternatives to traditional treatments like Tamoxifen, and ongoing research aims to enhance their use in preoperative settings and for chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endocrine therapy for breast cancer: an overview. Cheung, KL.[2022]

Adjuvant endocrine treatment is crucial for postmenopausal women with hormone receptor-positive breast cancer, with options including tamoxifen and aromatase inhibitors, each having unique side effects.

For premenopausal women, tamoxifen is the standard treatment, and ongoing research is exploring the potential benefits of adding ovarian suppression to enhance treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for early-stage breast cancer. Burstein, HJ., Griggs, JJ.[2010]

Tamoxifen has been the standard treatment for premenopausal women with breast cancer for over 30 years, but adding ovarian function suppression to endocrine therapy can lead to better outcomes for selected patients.

Extended therapy duration is becoming a new standard of care for high-risk patients, and ongoing research is focused on developing new drugs to overcome endocrine resistance, highlighting the importance of personalized treatment plans that consider side effects and quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Modern Landscape of Endocrine Therapy for Premenopausal Women with Breast Cancer. Rossi, L., Pagani, O.[2020]

Endocrine therapy is crucial for treating endocrine-sensitive breast cancer, significantly lowering recurrence rates and mortality when administered for 5 years in the adjuvant setting.

Tamoxifen is preferred for premenopausal women, while aromatase inhibitors are standard for postmenopausal women; however, managing side effects is essential to ensure patient compliance and improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Endocrine therapy in breast cancer: efficacy and adverse events]. Odermatt, R., Wolfer, A., Zaman, K.[2013]

Endocrine therapy is essential for treating premenopausal women with early-stage hormone receptor-positive breast cancer, but there is still uncertainty about the best strategies for using tamoxifen and estrogen deprivation alongside chemotherapy.

Research is ongoing to find better markers for predicting how well patients will respond to endocrine therapy and to understand the unique side effects that young women may experience from this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant hormonal therapy for premenopausal women with breast cancer. Brown, RJ., Davidson, NE.[2015]

In a study of 81 patients with metastatic breast cancer, Exemestane (EXE) demonstrated moderate efficacy as a second-line treatment, achieving a clinical benefit rate (CBR) of 39% after Anastrozole (ANA) failed.

Patients with only bone and soft tissue metastases had better outcomes with EXE compared to those with visceral metastases, suggesting that EXE may be particularly effective in certain metastatic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examination of the use of Exemestane in patients with metastatic breast cancer. Takashima, S., Kiyoto, S., Takahashi, M., et al.[2016]

Fulvestrant is a selective estrogen receptor down-regulator (SERD) that has shown significant efficacy and a strong safety profile in treating postmenopausal women with hormone-receptor positive metastatic breast cancer.

Combining fulvestrant with targeted therapies has demonstrated increased effectiveness, suggesting it may become a new standard treatment, with ongoing clinical trials (FALCON and FEVEX) expected to provide further insights into its optimal use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of fulvestrant in the treatment of postmenopausal metastatic breast cancer patients. Poggio, F., Lambertini, M., Blondeaux, E., et al.[2018]

The combination of S-1 and fulvestrant showed significantly enhanced antitumor activity in estrogen-responsive breast cancer (MCF-7) compared to either treatment alone, indicating a potential new effective therapy.

Fulvestrant not only inhibited tumor growth but also significantly down-regulated estrogen and progesterone receptor levels when combined with S-1, suggesting a mechanism that may improve treatment outcomes in hormone-responsive breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estrogen Down-regulator Fulvestrant Potentiates Antitumor Activity of Fluoropyrimidine in Estrogen-responsive MCF-7 Human Breast Cancer Cells. Nukatsuka, M., Saito, H., Noguchi, S., et al.[2020]

Citations

1. roche.com roche.com/media/releases/med-cor-2025-10-18

Roche's phase III evERA data showed giredestrant ... Giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in ITT and ESR1-mutated populations, ...

2. prnewswire.com prnewswire.com/news-releases/the-results-of-the-empress-study-show-the-activity-of-giredestrant-in-reducing-tumor-proliferation-in-erher2--breast-cancer-at-early-stages-without-the-need-for-ovarian-function-suppression-302588871.html

The results of the EMPRESS study show the activity ... "The results of the EMPRESS study are very promising, as they indicate greater activity of giredestrant compared to tamoxifen in slowing tumor ...

3. oncology-central.com oncology-central.com/esmo-2025-giredestrant-everolimus-improves-progression-free-survival-in-metastatic-er-her2-breast-cancer/

ESMO 2025: Giredestrant-everolimus improves ... Patients with ER+ HER2- advanced breast cancer showed improved progression-free survival when treated with an oral combination regimen ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01500

Giredestrant for Estrogen Receptor–Positive, HER2- ... Giredestrant is well tolerated, and has shown encouraging antitumor activity in aBC as a monotherapy and in combination with palbociclib, ...

5. onclive.com onclive.com/view/dr-mayer-on-efficacy-data-with-giredestrant-plus-everolimus-in-er-her2-breast-cancer

Dr Mayer on Efficacy Data With Giredestrant Plus ... Findings presented at the 2025 ESMO Congress showed that giredestrant plus everolimus significantly reduced the risk of progression or death ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04436744

NCT04436744 | A Study to Evaluate the Efficacy, Safety ... This is a randomized, multicenter, open-label, two-arm, Phase II study to evaluate the efficacy, safety, and pharmacokinetics of giredestrant versus ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10870118/

Phase Ia/b Study of Giredestrant ± Palbociclib and ... Conclusions: Giredestrant was well tolerated and clinically active in patients who progressed on prior endocrine therapy. Results warrant further evaluation of ...