Giredestrant for Advanced Breast Cancer

Not currently recruiting at 186 trial locations

Overseen By Reference Study ID Number: WO42312 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hoffmann-La Roche

Must be taking: LHRH agonists

Must not be taking: Investigational therapies

Disqualifiers: CNS metastases, Cardiac disease, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to approximately 36 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called giredestrant for individuals with advanced breast cancer that is estrogen receptor-positive and HER2-negative. Researchers aim to determine if giredestrant is more effective than the usual hormone treatments prescribed by doctors. Participants will receive either giredestrant or a typical hormone therapy chosen by their doctor, such as fulvestrant (also known as Faslodex) or an aromatase inhibitor. This trial may suit women whose breast cancer has worsened after one or two treatments and who lack surgical options for a cure. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking a selective estrogen receptor degrader (SERD) other than fulvestrant, you may need to stop, as prior treatment with SERDs is an exclusion criterion.

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

Research has shown that giredestrant, a treatment for some advanced breast cancers, is generally well-tolerated by patients. Studies have found its safety profile to be similar to other common hormone-related treatments, indicating comparable risks and side effects to those already familiar to many doctors and patients.

Patients in previous studies responded well to giredestrant, experiencing side effects typical of hormone therapies. This suggests that giredestrant is a safe option with manageable side effects.

For those considering joining a clinical trial, this information may provide reassurance about the treatment's safety. It is always important to discuss potential risks and benefits with a healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for breast cancer?

Giredestrant is unique because it represents a new class of oral selective estrogen receptor degraders (SERDs) for advanced breast cancer. Most treatments for this condition, like aromatase inhibitors and fulvestrant, work by reducing estrogen levels or blocking estrogen receptors. However, giredestrant goes a step further by actively degrading the estrogen receptor itself, potentially offering a more effective way to prevent cancer cell growth. Researchers are excited about giredestrant because its novel mechanism could lead to better outcomes for patients who have limited options with existing therapies.

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

Research shows that giredestrant has promising results for treating estrogen receptor-positive, HER2-negative advanced breast cancer. In this trial, some participants will receive giredestrant, which has demonstrated effectiveness in shrinking tumors and is generally well-tolerated. Studies found that combining giredestrant with everolimus can reduce the risk of cancer progression or death by up to 62% in some patients. This makes giredestrant an appealing option for those with advanced breast cancer seeking new treatments. Meanwhile, other participants in this trial will receive a physician's choice of endocrine monotherapy, limited to fulvestrant or an aromatase inhibitor. ^{1 2 4 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 postmenopausal or premenopausal women with ER-positive, HER2-negative advanced breast cancer who've had 1-2 systemic therapies but not more than one targeted therapy. They must have good organ function and agree to LHRH agonist therapy if premenopausal. Exclusions include active heart disease, uncontrolled brain metastases, life-threatening visceral spread, prior SERD treatment (except fulvestrant), investigational drug use within 28 days, or being pregnant/breastfeeding.

Inclusion Criteria

My breast cancer cannot be cured with surgery or radiation.

I am willing to undergo hormone therapy if I am a premenopausal or perimenopausal woman, or a man.

My tumor is ER-positive and HER2-negative.

Exclusion Criteria

I have not been treated with SERDs, except for fulvestrant which I stopped at least 28 days ago.

Treatment with any investigational therapy within 28 days prior to randomization

My cancer has spread to vital organs and could cause serious health issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive giredestrant or physician's choice of endocrine monotherapy

Up to approximately 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aromatase Inhibitor (Physician's Choice)
• Fulvestrant
• Giredestrant

Trial Overview The study compares the effectiveness of Giredestrant against a physician's choice of endocrine monotherapy in patients with certain types of advanced breast cancer. It's an open-label Phase II trial where participants are randomly assigned to receive either Giredestrant or another hormone therapy chosen by their doctor.

How Is the Trial Designed?

Group I: Giredestrant Experimental Treatment 2 Interventions

Group II: Physician Choice of Endocrine Monotherapy Active Control 2 Interventions

The physician choice of endocrine monotherapy will be limited to fulvestrant or an aromatase inhibitor.

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

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

The EFECT trial is the first Phase III study showing that fulvestrant is an effective treatment option for postmenopausal women with advanced breast cancer who have progressed on aromatase inhibitors, demonstrating similar efficacy to exemestane.

Both fulvestrant and exemestane had comparable safety profiles, with no significant differences in adverse events reported, indicating that fulvestrant can be a viable alternative after AI failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant: expanding the endocrine treatment options for patients with hormone receptor-positive advanced breast cancer. Chia, S., Gradishar, W.[2018]

Faslodex (fulvestrant) is a novel selective estrogen receptor down-regulator (SERD) that effectively targets and degrades the estrogen receptor, offering a new treatment option for advanced breast cancer, especially in cases where tumors have become resistant to tamoxifen.

Unlike tamoxifen, which can lead to resistance and has risks such as endometrial carcinoma, Faslodex provides a 'pure' antiestrogen effect without agonistic activity, making it a promising alternative for both advanced and early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Faslodex(TM) for the treatment of breast cancer. Smolnikar, K.[2019]

In a study involving 587 postmenopausal women with advanced breast cancer, fulvestrant showed similar efficacy to tamoxifen in patients with hormone receptor-positive tumors, with no significant differences in time to progression (TTP) or objective response rates.

While tamoxifen had a slightly better overall efficacy in the general population, both treatments were well tolerated, indicating that fulvestrant can be a viable option for patients with ER+ and/or PgR+ tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of fulvestrant versus tamoxifen for the treatment of advanced breast cancer in postmenopausal women previously untreated with endocrine therapy: a multinational, double-blind, randomized trial. Howell, A., Robertson, JF., Abram, P., et al.[2022]

Fulvestrant (Faslodex) is as effective as anastrozole (Arimidex) for treating advanced breast cancer in postmenopausal women, with similar objective response rates across different patient subgroups.

Both treatments provided comparable clinical benefits, making fulvestrant a valuable option for patients with visceral metastases who have not responded to previous endocrine therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant (Faslodex) versus anastrozole for the second-line treatment of advanced breast cancer in subgroups of postmenopausal women with visceral and non-visceral metastases: combined results from two multicentre trials. Mauriac, L., Pippen, JE., Quaresma Albano, J., et al.[2019]

In a phase II study involving 205 postmenopausal women with advanced hormone receptor-positive breast cancer, high-dose fulvestrant (500 mg/month) showed a clinical benefit rate (CBR) similar to anastrozole (72.5% vs. 67.0%), indicating comparable effectiveness as first-line therapy.

Fulvestrant high-dose was associated with a significantly longer time to progression (TTP) compared to anastrozole, suggesting it may provide a more durable response in treatment, while both therapies had similar safety profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of fulvestrant 500 mg versus anastrozole 1 mg as first-line treatment for advanced breast cancer: results from the FIRST study. Robertson, JF., Llombart-Cussac, A., Rolski, J., et al.[2022]

Aromatase inhibitors (AIs) like letrozole and anastrozole are effective first-line treatments for postmenopausal women with metastatic breast cancer, showing better efficacy and fewer side effects compared to the traditional antiestrogen tamoxifen.

Clinical studies and preclinical models indicate that AIs significantly suppress estrogen synthesis, leading to improved patient outcomes and suggesting potential benefits when combined with other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy. Brodie, AH., Mouridsen, HT.[2019]

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. dana-farber.org dana-farber.org/newsroom/news-releases/2025/novel-treatment-combination-improves-progression-free-survival-in-metastatic-estrogen-receptor-positive-her-2-negative-breast-cancer

Novel Treatment Combination Improves Progression-Free ... Patients with estrogen-receptor positive HER2 negative advanced breast cancer showed significantly improved progression-free survival when ...

3. onclive.com onclive.com/view/giredestrant-everolimus-extends-pfs-for-er-her2--advanced-breast-cancer

Giredestrant/Everolimus Extends PFS for ER+, HER2 Giredestrant plus everolimus improved progression-free survival in ER-positive, HER2-negative advanced breast cancer after a prior CDK4/6 ...

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/NCT05306340

NCT05306340 | A Study Evaluating the Efficacy and Safety ... This Phase III, randomized, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus everolimus compared with the ...

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

Phase Ia/b Study of Giredestrant ± Palbociclib and ... In this phase Ia/b study of single-agent giredestrant in patients with ER+, HER2− locally advanced/metastatic breast cancer, giredestrant was well tolerated; ...