Combination Therapy for Breast Cancer

Recruiting at 40 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment combinations for breast cancer that has spread or cannot be removed surgically. It targets individuals with estrogen receptor-positive (ER+) breast cancer that has become resistant to current treatments, such as CDK4/6 inhibitors or anti-HER2 therapies. The trial includes different groups to test various drug combinations, aiming to find better options for those whose cancer has progressed despite previous treatments. Individuals whose breast cancer has continued to grow after certain treatments, and who meet specific medical profiles, such as having an ER+ tumor, might be suitable candidates for this study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive potentially groundbreaking treatment.

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.

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

Previous studies have shown that abemaciclib has a predictable and manageable safety profile. Most side effects are mild and can be controlled by adjusting the dose if needed. Similarly, patients have tolerated palbociclib well, though some experienced a drop in white blood cells, the most common reaction. Ribociclib also presents manageable side effects, with some patients experiencing decreases in white blood cells, but these effects are often reversible.

These treatments belong to the same group of drugs and have been used in various combinations with other therapies. Safety data from past studies indicate that these drugs are generally safe when managed properly. However, each person's experience can differ, so discussing any concerns with the trial team is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they offer a range of innovative approaches targeting different pathways. Unlike traditional therapies such as chemotherapy, these investigational treatments include drugs like Giredestrant, which is a selective estrogen receptor degrader, offering a novel mechanism of action. Some combinations explore the potential of adding CDK4/6 inhibitors like Palbociclib or Ribociclib, which help prevent cancer cell division. Other combinations incorporate drugs like Abemaciclib and Atezolizumab, aiming to boost the immune system's ability to fight cancer. These diverse strategies provide hope for more personalized and effective treatment options for patients with breast cancer.

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

Research has shown that abemaciclib, one of the treatments in this trial, can extend the lives of people with metastatic breast cancer. Studies found it improved survival rates when used as the first treatment. Another drug under study, palbociclib, slowed the disease by 30% when combined with hormone therapy in advanced HR-positive/HER2-negative breast cancer. Ribociclib, also part of this trial, effectively reduced the chance of cancer recurrence by 28% over five years in early-stage breast cancer patients. These findings suggest that the combination treatments in this trial could benefit participants with certain types of breast cancer. ^{3 6 7 8 9}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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 (ESR1m enriched) Experimental Treatment 2 Interventions

ESR1m stands for estrogen receptor mutation.

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

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

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

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

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

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

Group XVI: 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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41092644/

metastatic breast cancer: A propensity-matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

2. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... In high-risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, an adjuvant ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04031885

NCT04031885 | A Study of Abemaciclib (LY2835219) in ... The reason for this study is to compare the efficacy of abemaciclib, in combination with fulvestrant, to that of physician's choice of chemotherapy in women ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

5. verzenio.lilly.com verzenio.lilly.com/hcp/efficacy-early-breast-cancer

Verzenio® + ET for Early Breast Cancer | Efficacy - Eli Lilly At Month 24, Verzenio plus ET was 92.6% vs ET alone at 89.4%—a 2-year delta of 3.2%. At Month 36, Verzenio plus ET was 88.9% vs ET alone at 83.7%—a 3-year delta ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf

VERZENIO® (abemaciclib) tablets, for oral use The safety of VERZENIO was evaluated in MONARCH 1, a single-arm, open-label, multicenter study in 132 women with measurable HR-positive, HER2-negative ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7990838/

Safety and efficacy of abemaciclib plus endocrine therapy ... Abemaciclib in combination with endocrine therapy (ET) has demonstrated significant efficacy benefits in HR+ , HER2− advanced breast cancer patients.

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/208855Orig1s000RiskR.pdf

208855Orig1s000 - accessdata.fda.gov 5 Risk Assessment & Safe-Use Conditions. The safety profile of abemaciclib was initially established by the safety data from the Phase 3 MONARCH.

9. sciencedirect.com sciencedirect.com/science/article/pii/S0923753422003830

Adjuvant abemaciclib combined with endocrine therapy for ... The safety profile of adjuvant abemaciclib has now also been established and is considered predictable, manageable, and acceptable in a high-risk EBC population ...