Giredestrant + Everolimus for Advanced or Metastatic Breast Cancer

Not currently recruiting at 293 trial locations

Overseen By Reference Study ID Number: ML43171 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Genentech, Inc.

Must be taking: LHRH agonists

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Chemotherapy, CNS metastases, Cardiac 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: Up to 42 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of treatments for advanced breast cancer that is estrogen receptor-positive and HER2-negative. It compares the effectiveness of giredestrant, a potential new drug, with everolimus against the usual endocrine therapy plus everolimus. The study aims to find better ways to manage breast cancer in patients who have already tried certain therapies, such as CDK4/6 inhibitors and endocrine treatments. It seeks participants with advanced breast cancer that has spread and who have experienced progression after these prior treatments. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to advancing breast cancer treatment options.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take strong CYP3A4 inhibitors or inducers within 14 days before starting the trial. If you have been on certain investigational therapies, you need to wait 28 days before joining.

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

A previous study showed that patients with breast cancer who took giredestrant with everolimus experienced a longer time before their cancer worsened compared to other treatments. This finding is encouraging as it suggests the treatment's effectiveness.

Regarding safety, advanced trials are testing giredestrant, indicating some evidence of its tolerability. Everolimus is already approved for other uses, providing extensive safety information. However, researchers are still studying the safety of using both drugs together.

Overall, the treatment appears promising, but like any new combination, it may have side effects. Understanding these is crucial before deciding to join a trial. ^{1 2 3 4 5}

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

Researchers are excited about Giredestrant because, unlike traditional treatments for advanced or metastatic breast cancer, it is a selective estrogen receptor degrader (SERD) that works by targeting and breaking down the estrogen receptor on cancer cells. This is different from standard treatments like fulvestrant or tamoxifen which mainly block estrogen receptors. The combination of Giredestrant with Everolimus could potentially enhance its effectiveness by also targeting the mTOR pathway, offering a dual approach to tackling cancer cell growth and survival. This innovation in mechanism may provide a more potent option for patients, especially those who have not responded well to current therapies.

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

Research has shown that the combination of giredestrant and everolimus, tested in this trial, holds promise for treating certain advanced breast cancers. Earlier studies found that this combination reduced the risk of cancer progression or death by 44% in all patients and by 62% in those with specific genetic changes, allowing patients to live longer without their cancer worsening. This trial will compare the giredestrant plus everolimus combination with the physician's choice of endocrine therapy plus everolimus for estrogen receptor-positive and HER2-negative breast cancer. These findings suggest that this treatment could be a viable option for patients who have not succeeded with other therapies. ^{1 3 6 7 8}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Genentech, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced breast cancer that's ER-positive, HER2-negative, and has spread. They must have tried CDK4/6 inhibitors and endocrine therapy before. The cancer should be measurable or show bone metastases. Participants need to be relatively healthy (good performance status) and premenopausal women or men must use LHRH agonists.

Inclusion Criteria

My tumor is positive for estrogen receptors and negative for HER2.

I am fully active or can carry out light work.

My breast cancer cannot be surgically removed and is not treatable with curative intent.

Exclusion Criteria

I don't have any serious health issues that would stop me from safely completing the study.

I have not had any cancer other than breast cancer in the last 5 years, except for certain low-risk types or those treated with surgery.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive giredestrant plus everolimus or the physician's choice of endocrine therapy plus everolimus

Up to 42 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after treatment discontinuation

What Are the Treatments Tested in This Trial?

Interventions

• Everolimus
• Fulvestrant
• Giredestrant

Trial Overview The study compares the effectiveness of Giredestrant plus Everolimus against standard endocrine therapies plus Everolimus in patients who've previously used CDK4/6 inhibitors. It's a Phase III trial where participants are randomly assigned to either treatment group.

How Is the Trial Designed?

Group I: Giredestrant plus Everolimus Experimental Treatment 4 Interventions

Group II: Physician's Choice of Endocrine Therapy plus Everolimus Active Control 6 Interventions

The physician's choice of endocrine therapy is defined as either exemestane, fulvestrant, or tamoxifen.

Everolimus is already approved in United States, European Union for the following indications:

Approved in United States as Afinitor for:

• Advanced renal cell carcinoma
• Subependymal giant cell astrocytoma
• Progressive neuroendocrine tumors of pancreatic origin
• Advanced hormone receptor-positive, HER2-negative breast cancer
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in European Union as Votubia for:

• Subependymal giant cell astrocytoma
• Renal angiomyolipoma
• Tuberous sclerosis complex-associated partial-onset seizures

Approved in United States as Zortress for:

• Prevention of organ rejection in kidney transplant patients

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Published Research Related to This Trial

In a study of 348 postmenopausal women with hormone receptor-positive metastatic breast cancer, everolimus-based therapy (EVE) showed significantly longer progression-free survival (PFS) compared to fulvestrant monotherapy (FUL), with a hazard ratio of 0.71.

EVE was particularly effective for patients who had previously progressed on nonsteroidal aromatase inhibitors, indicating its potential as a preferred treatment option in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer. Hao, Y., Lin, PL., Xie, J., et al.[2018]

In a phase II trial involving 31 postmenopausal women with metastatic ER-positive breast cancer who had previously failed aromatase inhibitors, the combination of fulvestrant and everolimus showed a median time to progression of 7.4 months and a clinical benefit rate of 49%.

The treatment was associated with manageable side effects, with most adverse events being mild to moderate, but 32% of patients exhibited de novo resistance, highlighting the need for biomarker analysis to identify those who may benefit most from this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of combined fulvestrant and everolimus in patients with metastatic estrogen receptor (ER)-positive breast cancer after aromatase inhibitor (AI) failure. Massarweh, S., Romond, E., Black, EP., et al.[2021]

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/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 ...

4. cancernetwork.com cancernetwork.com/view/giredestrant-combo-significantly-boosts-pfs-in-er-advanced-breast-cancer

Giredestrant Combo Significantly Boosts PFS in ER+ ... Data from the phase 3 evERA trial show a trend toward improved overall survival with giredestrant plus everolimus in this breast cancer ...

5. 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 physician's ...

6. 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 ...

7. 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 ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.1059

Interim analysis (IA) of the giredestrant (G) + everolimus ... acelERA Breast Cancer (BC): Phase II study evaluating efficacy and safety of giredestrant (GDC-9545) versus physician's choice of endocrine ...