Giredestrant + Everolimus for Advanced or Metastatic Breast Cancer

Recruiting at 261 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

320 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if a combination of giredestrant and everolimus works better than other hormone treatments plus everolimus in patients with advanced breast cancer who have already tried other treatments. The drugs work by blocking estrogen receptors and a growth pathway in cancer cells. Everolimus has been shown to improve outcomes in breast cancer patients when combined with hormonal treatments.

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.

What data supports the effectiveness of the drug combination of Giredestrant and Everolimus for advanced or metastatic breast cancer?

Research shows that combining Everolimus with endocrine therapy like Fulvestrant improves progression-free survival in women with hormone receptor-positive, HER2-negative metastatic breast cancer, especially after resistance to other treatments. This suggests that Everolimus can enhance the effectiveness of hormone therapies in similar breast cancer cases. ^{1 2 3 4 5}

Is the combination of Giredestrant and Everolimus safe for treating advanced breast cancer?

Everolimus, when combined with other therapies for advanced breast cancer, has been generally well tolerated, but it can cause side effects like mouth sores, fatigue, rash, anemia (low red blood cell count), diarrhea, high blood sugar, and lung inflammation. These side effects are common in cancer treatments, and managing them is important for patient well-being. ^{2 3 6 7 8}

What makes the drug combination of Giredestrant, Everolimus, and Fulvestrant unique for treating advanced breast cancer?

This drug combination is unique because it combines Giredestrant, a new type of estrogen receptor degrader, with Everolimus, which targets a specific pathway (mTOR) involved in cancer growth, and Fulvestrant, which also degrades estrogen receptors. This approach aims to overcome resistance to previous hormone therapies and may offer a more effective treatment option for patients with advanced breast cancer. ^{1 4 6 9 10}

Research Team

Clinical Trials

Principal Investigator

Genentech, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Everolimus Boosts Endocrine Therapy for Breast Cancer. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102. [2022]

4. Netherlands 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. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Everolimus Added to Adjuvant Endocrine Therapy in Patients With High-Risk Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Primary Breast Cancer. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase I Trial of Everolimus and Capecitabine in Metastatic HER2- Breast Cancer. [2018]

7. Cyprus pubmed.ncbi.nlm.nih.gov

Efficacy of everolimus combined with endocrine therapy in HR-positive/HER-2-negativeadvanced breast cancer. [2021]

8. Germany pubmed.ncbi.nlm.nih.gov

Management of adverse events in patients with hormone receptor-positive breast cancer treated with everolimus: observations from a phase III clinical trial. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Palbociclib Combinations in Hormone Receptor-Positive Metastatic Breast Cancer Patients After Prior Everolimus Treatment. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

A Randomized Trial of Fulvestrant, Everolimus, and Anastrozole for the Front-line Treatment of Patients with Advanced Hormone Receptor-positive Breast Cancer, SWOG S1222. [2023]