Combination Therapy for Breast Cancer

Recruiting at 31 trial locations

Overseen By Reference Study ID Number: CO42867 https://forpatients.roche.com/

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must be taking: Endocrine therapy

Must not be taking: CYP3A4 inhibitors, Corticosteroids

Disqualifiers: Active infection, Cardiac disease, CNS metastases, 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)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 weeks

316 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing new treatments for advanced breast cancer in patients whose cancer has not responded to previous treatments. It aims to find more effective drug combinations for these patients. One of the treatments being tested is Lapatinib, which is being evaluated both for patients whose cancer has returned and as an initial treatment option in combination with chemotherapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting, such as strong CYP3A4 inhibitors or inducers, and any systemic treatment for breast cancer within 2 weeks of starting the trial. If you are on these medications, you may need to stop them before participating.

What data supports the effectiveness of the drug combination therapy for breast cancer?

Research shows that adding abemaciclib, a CDK4/6 inhibitor, to endocrine therapy significantly improves progression-free survival and response rates in certain types of breast cancer, making it a valuable treatment option. This combination is particularly effective for patients with hormone receptor positive (HR+) and HER2-negative breast cancer, both in early and advanced stages. ^{1 2 3 4 5}

Is the combination therapy for breast cancer safe for humans?

Abemaciclib, when used with endocrine therapy for certain types of breast cancer, has been found to have a tolerable safety profile, with common side effects including diarrhea, infections, and neutropenia (low white blood cell count). These side effects are generally manageable. ^{2 4 5 6 7}

What makes the combination therapy for breast cancer unique?

This combination therapy is unique because it includes multiple drugs like Abemaciclib, which is a CDK4/6 inhibitor that helps prevent cancer cells from growing, and other targeted therapies like Trastuzumab-deruxtecan, which specifically targets cancer cells with certain proteins. This multi-drug approach aims to improve effectiveness by attacking the cancer in different ways. ^{1 2 4 5 8}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for postmenopausal women with advanced or metastatic ER-positive, HER2-negative breast cancer that worsened after CDK4/6 inhibitor treatment. It's also for those with ER-positive, HER2-positive breast cancer resistant to anti-HER2 therapies and trastuzumab-and-taxane-based therapy. Participants must have a life expectancy of at least 3 months and be able to provide a tumor sample.

Inclusion Criteria

My blood and organs are functioning well.

My cancer worsened after hormone therapy including a CDK4/6 inhibitor.

My blood thinner medication dose has been stable.

Exclusion Criteria

I have had major surgery on my stomach or small bowel, or I have a chronic condition causing frequent severe diarrhea.

I have not received a live-virus vaccine in the last 28 days.

I haven't had major heart issues or strokes in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various treatment combinations based on their cohort, including Giredestrant with other agents like Abemaciclib, Atezolizumab, and others

12-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term as new treatment arms become available

Long-term

Treatment Details

Interventions

• Abemaciclib
• Ado-trastuzumab emtansine
• Lapatinib
• Neratinib
• Palbociclib
• Pyrotinib
• Ribociclib
• Trastuzumab-deruxtecan
• Tucatinib

Trial Overview The study tests various drug combinations (like Atezolizumab, Palbociclib) in two cohorts based on the type of breast cancer. Patients are randomly assigned to different treatments which may change if they experience disease progression or unacceptable side effects during the initial stage.

Participant Groups

Group I: Cohort 3: Giredestrant + Inavolisib + Ribociclib Experimental Treatment 3 Interventions

Group II: Cohort 3: Giredestrant + Inavolisib + Palbociclib Experimental Treatment 3 Interventions

Group III: Cohort 3: Giredestrant + Inavolisib + Abemaciclib Experimental Treatment 3 Interventions

Group IV: Cohort 2: Giredestrant + PH FDC SC + Palbociclib Experimental Treatment 3 Interventions

Group V: Cohort 2: Giredestrant + PH FDC SC + Abemaciclib Experimental Treatment 3 Interventions

Group VI: Cohort 1: Giredestrant + Samuraciclib Experimental Treatment 2 Interventions

Group VII: Cohort 1: Giredestrant + Ribociclib Experimental Treatment 2 Interventions

Group VIII: Cohort 1: Giredestrant + Ipatasertib Experimental Treatment 2 Interventions

Group IX: Cohort 1: Giredestrant + Inavolisib Experimental Treatment 2 Interventions

Group X: Cohort 1: Giredestrant + Everolimus Experimental Treatment 2 Interventions

Group XI: Cohort 1: Giredestrant + Atezolizumab Experimental Treatment 2 Interventions

Group XII: Cohort 1: Giredestrant + Abemaciclib + Atezolizumab Experimental Treatment 3 Interventions

Group XIII: Cohort 1: Giredestrant + Abemaciclib Experimental Treatment 2 Interventions

Group XIV: Cohort 2: Giredestrant + PH FDC SC Active Control 2 Interventions

Group XV: Cohort 1: Giredestrant Monotherapy Active Control 1 Intervention

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

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast 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

The addition of CDK4 and 6 inhibitors (like abemaciclib, palbociclib, or ribociclib) to endocrine therapy significantly improves progression-free survival and response rates in patients with HR+ and HER2- metastatic breast cancer, establishing these inhibitors as a new standard of care.

Exploratory analyses suggest that abemaciclib may be particularly beneficial for women with poor prognosis indicators, although further confirmation is needed for these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. Martin, M., Garcia-Saenz, JA., Manso, L., et al.[2021]

Interim results from the MONARCH3 study show that abemaciclib, a CDK4/6 inhibitor, is an effective first-line treatment for advanced ER-positive, HER2-negative breast cancer.

Patients receiving abemaciclib in combination with letrozole experienced significantly improved progression-free survival compared to those receiving a placebo with endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

A new ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed to effectively monitor abemaciclib levels in patients with advanced breast cancer, showing high accuracy and precision in quantification.

This method allows for robust therapeutic drug monitoring (TDM) of abemaciclib, which can help personalize treatment and improve adherence in patients, addressing challenges in the emerging field of oral antitumor therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. Habler, K., Vogeser, M., Teupser, D.[2022]

Abemaciclib combined with endocrine therapy (ET) significantly improves quality-adjusted life years (QALYs) in patients with high-risk hormone receptor positive, HER2-negative early breast cancer, with an increase of 0.99 QALYs compared to ET alone.

The treatment is considered cost-effective in Italy, with an incremental cost-effectiveness ratio of €22,651 per QALY gained, and a 99% likelihood of being cost-effective at a threshold of €30,000 per QALY.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. Davie, A., Traoré, S., Giovannitti, M., et al.[2023]

In a phase III trial, abemaciclib combined with endocrine therapy significantly reduced the risk of breast cancer recurrence in patients with hormone receptor positive (HR+), HER2-negative, node-positive early breast cancer, regardless of prior chemotherapy or tumor characteristics.

The combination treatment was generally well-tolerated, with manageable side effects such as diarrhea, infections, and neutropenia, making it a valuable option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. Fung, S., Blair, HA.[2023]

Abemaciclib, used for treating advanced breast cancer, was generally well tolerated, with the most common adverse event being diarrhea, affecting 42.8% of patients, which was manageable with medications and dose adjustments.

Importantly, dose reductions or early onset of adverse events like diarrhea and neutropenia did not negatively impact progression-free survival, indicating that patients can continue treatment effectively despite these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. Rugo, HS., Huober, J., García-Sáenz, JA., et al.[2023]

In a study of 396 female patients with hormone receptor positive, HER2-negative metastatic breast cancer receiving CDK4 and 6 inhibitors, the most common adverse events were neutropenia, diarrhea, and fatigue, with varying frequencies depending on the specific drug used.

The study found that while the overall incidence of adverse events was lower than in clinical trials, the rates of dose reductions and treatment holds due to these events were higher, suggesting that clinicians may be actively managing side effects to help patients continue their therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. Price, GL., Sudharshan, L., Ryan, P., et al.[2022]

In a pooled analysis of 1152 patients from the MONARCH 2 and MONARCH 3 studies, abemaciclib combined with endocrine therapy showed a consistent improvement in progression-free survival (PFS) across all age groups, indicating its efficacy in treating HR+, HER2- advanced breast cancer regardless of age.

Older patients experienced higher rates of clinically relevant side effects, such as diarrhea and nausea, but these were manageable with dose adjustments, suggesting that while safety concerns exist, the treatment remains effective for older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. Goetz, MP., Okera, M., Wildiers, H., et al.[2022]

References

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

Abemaciclib, a CDK4 and CDK6 inhibitor for the treatment of metastatic breast cancer. [2021]

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

First-Line Abemaciclib Effective in ER+ Breast Cancer. [2019]

3. Netherlands pubmed.ncbi.nlm.nih.gov

An UHPLC-MS/MS method for quantification of the CDK4/6 inhibitor abemaciclib in human serum. [2022]

4. Italy pubmed.ncbi.nlm.nih.gov

Cost-effectiveness analysis of abemaciclib with endocrine therapy (ET) versus ET alone for HR+, HER2-, node-positive, high-risk early breast cancer in Italy. [2023]

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

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Management of Abemaciclib-Associated Adverse Events in Patients with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Safety Analysis of MONARCH 2 and MONARCH 3. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Real world incidence and management of adverse events in patients with HR+, HER2- metastatic breast cancer receiving CDK4 and 6 inhibitors in a United States community setting. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of abemaciclib plus endocrine therapy in older patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer: an age-specific subgroup analysis of MONARCH 2 and 3 trials. [2022]