Giredestrant + Phesgo for Breast Cancer

Not currently recruiting at 388 trial locations

Overseen By Reference Study ID Number: WO43571 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Hoffmann-La Roche

Must be taking: LHRHa therapy

Must not be taking: Corticosteroids, CYP3A4 inhibitors

Disqualifiers: CNS metastases, Cardiac disease, others

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of combining giredestrant with Phesgo for treating advanced breast cancer that is both HER2-positive and ER-positive. It compares the use of Phesgo alone with the new combination of giredestrant and Phesgo to determine which is more effective after initial treatment. The trial targets individuals who have not received certain anti-cancer treatments for their advanced breast cancer and have stable disease following initial therapy. Those with advanced HER2-positive, ER-positive breast cancer that is inoperable may find this trial suitable. As a Phase 3 trial, it represents the final step before FDA approval, providing access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain treatments like strong CYP3A4 inhibitors or inducers, or if you are on chronic daily corticosteroids above a certain dose.

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

Research shows that giredestrant, when combined with Phesgo, has promising safety results. Earlier studies found giredestrant to be safe, with patients generally tolerating it well. Common side effects included mild fatigue and nausea, with no serious safety issues reported.

Phesgo, a combination of pertuzumab and trastuzumab, is already approved for treating certain types of breast cancer, indicating its safety has been well studied. Side effects of Phesgo can include diarrhea and hair loss, but these are usually manageable.

This trial examines the safety and effectiveness of using giredestrant and Phesgo together. It aims to determine if this combination works better than Phesgo alone for treating advanced breast cancer. ^{1 2 3 4}

Why are researchers excited about this trial's treatments?

Researchers are excited about Giredestrant combined with Phesgo for breast cancer because it represents a new approach compared to traditional treatments like hormone therapies and chemotherapy. Giredestrant is a next-generation selective estrogen receptor degrader (SERD), which works by targeting and breaking down estrogen receptors more effectively than older therapies, potentially offering better control of estrogen-driven cancer growth. By combining this with Phesgo, a convenient subcutaneous injection of pertuzumab and trastuzumab, patients may benefit from a more comprehensive and potentially more effective treatment regimen. Overall, these innovations offer the promise of improved efficacy, convenience, and outcomes for patients with breast cancer.

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

Research has shown that giredestrant, when combined with other treatments, yields promising results for breast cancer. It can reduce the risk of disease progression or death by up to 62% in some patients with advanced breast cancer. Giredestrant blocks and breaks down certain proteins that promote cancer growth. In this trial, one group of participants will receive maintenance therapy with giredestrant combined with Phesgo, a mix of other cancer drugs. Studies suggest that using giredestrant with other drugs can significantly extend the time patients live without their cancer worsening. These findings indicate that this combination could effectively treat HER2-positive, estrogen receptor-positive breast cancer. ^{2 3 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 HER2-positive, ER-positive advanced breast cancer that can't be removed by surgery. They should have completed at least four cycles of induction therapy without disease progression and have a heart function (LVEF) ≥50%. Participants must not have had certain previous cancer treatments, uncontrolled health issues, or been pregnant or breastfeeding.

Inclusion Criteria

I have completed at least four cycles of initial cancer treatment.

My cancer did not worsen after the initial treatment phase.

I have at least one tumor that can be measured or evaluated.

Exclusion Criteria

I haven't taken strong CYP3A4 inhibitors or inducers in the last 14 days or longer.

I have been treated with a SERD medication before.

All side effects from my previous cancer treatments have mostly gone away.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive Phesgo plus taxane-based chemotherapy

8-12 weeks

Maintenance Therapy

Participants receive either Phesgo or Giredestrant plus Phesgo

Up to 53 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Docetaxel
• Giredestrant
• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview The study compares the effectiveness and safety of Giredestrant combined with Phesgo versus Phesgo alone in patients after initial treatment with Phesgo plus taxane. It's a Phase III trial where participants are randomly assigned to one of two groups to see which treatment works better.

How Is the Trial Designed?

Group I: Induction Therapy: Phesgo plus Taxane-Based Chemotherapy Experimental Treatment 3 Interventions

Group II: Arm B, Maintenance Therapy: Giredestrant plus Phesgo Experimental Treatment 3 Interventions

Group III: Arm A, Maintenance Therapy: Phesgo Active Control 3 Interventions

Docetaxel is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in European Union as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Canada as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate Cancer

Approved in Japan as Taxotere for:

• Breast Cancer
• Non-small Cell Lung Cancer
• Gastric Cancer
• Head and Neck Cancer
• Prostate 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

Docetaxel has shown high efficacy in treating breast cancer, particularly in women who have not responded to anthracyclins or have liver metastases, with response rates superior to doxorubicin.

The side effects of docetaxel are comparable to those of doxorubicin, making it feasible to combine docetaxel with anthracyclins, which is currently being explored in clinical trials for first-line or adjuvant treatment settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Docetaxel (taxotere) for therapy of breast carcinoma. Highest effectiveness with moderate side effects]. von Minckwitz, G., Costa, SD.[2019]

The PERUSE study, involving 1436 patients with HER2-positive locally recurrent/metastatic breast cancer, confirmed that the combination of pertuzumab and trastuzumab with taxanes (docetaxel or paclitaxel) is safe and effective, with a median overall survival of 65.3 months and a median progression-free survival of 20.7 months.

The study found that paclitaxel is a valid alternative to docetaxel as the chemotherapy backbone, and identified risk factors that could help guide future clinical trials, particularly noting that patients with hormone receptor-positive disease had better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Final results from the PERUSE study of first-line pertuzumab plus trastuzumab plus a taxane for HER2-positive locally recurrent or metastatic breast cancer, with a multivariable approach to guide prognostication. Miles, D., Ciruelos, E., Schneeweiss, A., et al.[2022]

Pertuzumab, when combined with trastuzumab and docetaxel, received FDA accelerated approval for neoadjuvant treatment of HER2-positive breast cancer, showing a significant pathologic complete response rate of 39.3% compared to 21.5% for trastuzumab-docetaxel alone in a trial of 417 patients.

The most common side effects of the pertuzumab combination therapy included alopecia, diarrhea, nausea, and neutropenia, indicating that while effective, the treatment does have notable adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First FDA approval of neoadjuvant therapy for breast cancer: pertuzumab for the treatment of patients with HER2-positive breast cancer. Amiri-Kordestani, L., Wedam, S., Zhang, L., et al.[2022]

The ongoing PERUSE study, involving 1436 patients with HER2-positive advanced breast cancer, shows that the combination of pertuzumab, trastuzumab, and taxanes (docetaxel, paclitaxel, or nab-paclitaxel) is safe and effective, with a median progression-free survival (PFS) of 20.6 months and an overall response rate (ORR) of 80%.

Paclitaxel is a viable alternative to docetaxel, providing similar efficacy in terms of PFS and ORR, while presenting a more favorable safety profile with less febrile neutropenia and mucositis, despite a higher incidence of peripheral neuropathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE). Bachelot, T., Ciruelos, E., Schneeweiss, A., et al.[2023]

This study aims to systematically evaluate the efficacy and safety of the combination treatment of pertuzumab, trastuzumab, and docetaxel (PTD) for patients with HER2-positive breast cancer, using a comprehensive literature search across multiple databases and gray literature.

The outcomes of interest will include overall survival, complete response rates, cancer-specific survival, recurrence-free survival, disease-free survival, quality of life, and associated toxicities, providing a thorough assessment of PTD's effectiveness and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy of combination of pertuzumab, trastuzumab, and docetaxel for treatment of patients with HER2-positive breast cancer. Liu, YC., Ma, Y., An, N., et al.[2022]

Pertuzumab is an effective anti-HER2 monoclonal antibody that works by preventing HER2 from forming heterodimers, which reduces tumor cell growth and survival, particularly in HER2-positive metastatic breast cancer.

In the phase III CLEOPATRA trial involving a combination of pertuzumab, trastuzumab, and docetaxel, patients experienced significantly improved progression-free survival and overall survival compared to those receiving placebo, with an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab: a review of its use for first-line combination treatment of HER2-positive metastatic breast cancer. McCormack, PL.[2021]

The treatment with docetaxel led to complete remission of lung metastases in a 53-year-old woman with recurrent breast cancer, indicating its potential efficacy in chemotherapy for this condition.

While the patient experienced some adverse reactions, including grade 4 neutropenia and fluid retention, these were manageable, suggesting that docetaxel could be a tolerable option for patients with similar cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A case of recurrent breast cancer successfully treated with docetaxel]. Koshizuka, K., Hada, M., Muto, S., et al.[2018]

In a study of 81 HER2-positive breast cancer patients, the docetaxel + trastuzumab + pertuzumab regimen achieved a slightly higher complete pathological remission rate (51.2%) compared to the docetaxel + carboplatin + trastuzumab + pertuzumab regimen (44.7%).

The docetaxel + carboplatin regimen was associated with significantly higher rates of severe toxicity (68.4% vs 39.5%) and more frequent adjustments to the treatment plan, indicating that it may be less tolerated than the docetaxel + trastuzumab + pertuzumab regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual Anti-HER2 Blockade and Docetaxel With or Without Carboplatin as Neoadjuvant Regimen for Treatment of HER2-Positive Breast Cancer. Lin, B., Fan, J., Liu, F., et al.[2023]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In patients with HER2-positive metastatic breast cancer, the combination of pertuzumab, trastuzumab, and docetaxel significantly improved median overall survival to 56.5 months compared to 40.8 months with the placebo combination, indicating a 15.7-month advantage.

The addition of pertuzumab also enhanced progression-free survival by 6.3 months and extended the duration of response by 7.7 months, while maintaining long-term cardiac safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. Swain, SM., Baselga, J., Kim, SB., et al.[2022]

The addition of pertuzumab to the docetaxel and trastuzumab (TH) regimen for treating HER2-positive metastatic breast cancer increases overall survival from 5.78 to 8.38 life-years, but at a significantly higher cost of $60,846 compared to $24,109 for TH alone.

Despite the survival benefits, the cost-effectiveness analysis indicates that the pertuzumab plus TH regimen has a low probability (7.24%) of being cost-effective in Colombia, suggesting that the high cost may not justify the additional benefits in this healthcare context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Pertuzumab Plus Trastuzumab and Docetaxel Compared With Trastuzumab and Docetaxel in the Adjuvant Treatment of Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer in Colombia. Guevara-Cuellar, CA., Parody-Rúa, E., Rengifo-Mosquera, MP., et al.[2022]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT05296798

NCT05296798 | A Study to Evaluate the Efficacy and ... This Phase III, randomized, two-arm, open-label, multicenter study will evaluate the efficacy and safety of giredestrant plus Phesgo compared with Phesgo ...

3. 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 HER-2-negative advanced breast cancer showed significantly improved progression-free survival when ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38789924/

heredERA Breast Cancer: a phase III, randomized, open- ... Giredestrant, a novel oral selective ER antagonist and degrader, shows promising clinical activity and manageable safety across phase I-II trials of patients ...

5. onclive.com onclive.com/view/giredestrant-plus-everolimus-meets-coprimary-pfs-end-points-in-post-cdk-inhibitor-er-her2-breast-cancer

Giredestrant Plus Everolimus Meets Coprimary PFS End ... Giredestrant plus everolimus significantly improved progression-free survival in ER-positive, HER2-negative breast cancer post-CDK4/6 inhibitor ...

6. roche.com roche.com/media/releases/med-cor-2025-09-22

Positive phase III results show Roche's giredestrant ... Overall survival (OS) data were immature, but a clear positive trend was observed. Follow-up continues to the next OS analysis. The giredestrant ...

7. genentech-clinicaltrials.com genentech-clinicaltrials.com/en/trials/cancer/bc/a-study-to-evaluate-the-efficacy-and-safety-of-giredest-09790.html

Clinical Trial – Breast Cancer – Efficacy and Safety of G... This clinical trial aims to compare the effects, good or bad, of giredestrant with combined P + T versus combined P + T with or without hormone therapy in ...