Giredestrant + Phesgo for Breast Cancer

Recruiting at 331 trial locations

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

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing whether a combination of two drugs is more effective than one drug for patients with advanced breast cancer. The drugs work by blocking signals that help cancer cells grow. The study focuses on patients whose cancer cannot be cured with surgery or other local treatments.

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.

What data supports the effectiveness of the drug combination Giredestrant + Phesgo for breast cancer?

Research shows that adding pertuzumab to trastuzumab and docetaxel significantly improves survival in patients with HER2-positive breast cancer, both in early and metastatic stages. This suggests that the combination of these drugs can be effective in treating this type of breast cancer. ^{1 2 3 4 5}

Is the combination of Giredestrant + Phesgo safe for breast cancer treatment?

The combination of pertuzumab, trastuzumab, and docetaxel (components of Phesgo) has been studied for safety in breast cancer treatment. Common side effects include hair loss, diarrhea, nausea, and low white blood cell counts, which can be severe. However, the addition of pertuzumab did not worsen heart-related side effects in patients with low heart disease risk. ^{2 5 6 7 8}

What makes the drug Giredestrant + Phesgo unique for breast cancer treatment?

The drug Giredestrant + Phesgo is unique because it combines Giredestrant, a novel oral selective estrogen receptor degrader, with Phesgo, a combination of pertuzumab and trastuzumab, which are antibodies targeting the HER2 receptor. This combination aims to enhance the effectiveness of treatment by targeting both hormone receptor-positive and HER2-positive breast cancer pathways. ^{5 6 9 10 11}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Docetaxel (Chemotherapy)
• Giredestrant (Selective Estrogen Receptor Degrader (SERD))
• Paclitaxel (Chemotherapy)
• Pertuzumab (Monoclonal Antibodies)
• Trastuzumab (Monoclonal Antibodies)

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.

Participant Groups

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 Canada, Japan for the following indications:

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

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

References

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

Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. [2022]

2. United States 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. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

[Docetaxel (taxotere) for therapy of breast carcinoma. Highest effectiveness with moderate side effects]. [2019]

4. United States 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. [2022]

5. France pubmed.ncbi.nlm.nih.gov

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

6. England 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. [2022]

7. Japan pubmed.ncbi.nlm.nih.gov

[A case of recurrent breast cancer successfully treated with docetaxel]. [2018]

8. United States 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. [2023]

9. England 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). [2023]

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

Clinical efficacy of combination of pertuzumab, trastuzumab, and docetaxel for treatment of patients with HER2-positive breast cancer. [2022]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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