ARV-471 + Abemaciclib for Advanced Breast Cancer

Recruiting at 44 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pfizer

Must be taking: CDK4/6 inhibitors

Must not be taking: CYP3A inhibitors, QT prolongation drugs

Disqualifiers: Visceral crisis, Brain metastases, Cardiovascular diseases, others

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: 4

Duration: Until disease progression or unacceptable toxicity

37 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer. This study is seeking participants who have breast cancer that: * is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy * is sensitive to hormonal therapy (it is called estrogen receptor positive); and * is no longer responding to previous treatments This study is divided into separate sub-studies. For Sub-Study A: All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective. Participants will continue to take ARV-471 and abemaciclib until their cancer is no longer responding, or side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does exclude participants taking certain medications that affect liver enzymes or heart rhythm. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug Abemaciclib for advanced breast cancer?

Abemaciclib, when combined with other therapies, has been shown to improve progression-free survival in patients with advanced ER-positive, HER2-negative breast cancer, making it an effective treatment option. ^{1 2 3 4 5}

Is the combination of ARV-471 and Abemaciclib safe for humans?

Abemaciclib, also known as Verzenio, has been studied in various breast cancer treatments and is generally considered safe, with common side effects including diarrhea, infections, and low white blood cell counts. While specific safety data for the combination with ARV-471 is not provided, Abemaciclib alone has an acceptable safety profile in humans. ^{1 2 3 4 6}

What makes the drug ARV-471 + Abemaciclib unique for advanced breast cancer?

The combination of ARV-471 and Abemaciclib is unique because it pairs a novel selective estrogen receptor degrader (SERD) with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, potentially offering a new approach to target hormone receptor positive (HR+), HER2-negative advanced breast cancer by both degrading estrogen receptors and inhibiting cell cycle progression. ^{1 2 4 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for individuals with advanced or metastatic breast cancer that's estrogen receptor positive and not responding to previous treatments. Participants must have had up to two prior therapies, including one CDK4/6 inhibitor regimen, and should be in a stable condition without life-threatening visceral complications or recent other cancers.

Inclusion Criteria

I am fully active and can carry on all pre-disease activities without restriction.

At least 1 measurable lesion as defined by RECIST v1.1

My breast cancer is ER+ and HER2-, and cannot be removed by surgery.

Exclusion Criteria

I have had lung problems caused by medication before.

My condition is inflammatory breast cancer.

My kidney, liver, or bone marrow is not working properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ARV-471 and abemaciclib orally at home, with ARV-471 once daily and abemaciclib twice daily on a 28-day cycle

Until disease progression or unacceptable toxicity

Visits approximately every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 28 days after last dose

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to approximately 3 years

Treatment Details

Interventions

• Abemaciclib
• ARV-471

Trial Overview The study tests ARV-471 combined with abemaciclib in people with certain types of breast cancer. Both medications are taken orally at home—ARV-471 once daily and abemaciclib twice daily—and the effects on patients' health will be monitored regularly at the clinic.

Participant Groups

Group I: ARV-471 in combination with Abemaciclib Experimental Treatment 2 Interventions

ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle

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?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Arvinas Estrogen Receptor, Inc.

Industry Sponsor

Trials

19

Recruited

2,400+

Findings from Research

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 is an oral medication that inhibits cyclin-dependent kinases 4 and 6, specifically approved in the USA for treating advanced or metastatic breast cancer that is hormone receptor-positive and HER2-negative.

It is effective both as a combination therapy with fulvestrant for patients who have progressed after endocrine therapy and as a standalone treatment for those who have also undergone chemotherapy, highlighting its role in advanced cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Abemaciclib: First Global Approval. Kim, ES.[2019]

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]

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]

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]

In the MONARCH 3 study involving 493 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, abemaciclib combined with a nonsteroidal aromatase inhibitor significantly improved progression-free survival (PFS) to 28.18 months compared to 14.76 months for the placebo group.

The objective response rate (ORR) was also higher in the abemaciclib group at 61.0% versus 45.5% in the placebo group, with a tolerable safety profile, although some patients experienced grade ≥3 adverse events like neutropenia and diarrhea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. Johnston, S., Martin, M., Di Leo, A., et al.[2023]

In phase III clinical trials (MONARCH 2 and MONARCH 3), abemaciclib, a CDK4 & 6 inhibitor, significantly improved progression-free survival and overall survival in women with hormone receptor positive (HR+) and HER2-negative advanced breast cancer when used in combination with endocrine therapy.

Abemaciclib demonstrated a tolerable safety profile, making it a promising treatment option for patients who have progressed after previous endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. Masuda, N., Saji, S., Kawaguchi, T., et al.[2021]

References

1. France pubmed.ncbi.nlm.nih.gov

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

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

Abemaciclib: First Global Approval. [2019]

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

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

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. England pubmed.ncbi.nlm.nih.gov

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

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

MONARCH 3 final PFS: a randomized study of abemaciclib as initial therapy for advanced breast cancer. [2023]

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

Preclinical characterization of abemaciclib in hormone receptor positive breast cancer. [2019]

8. Japan pubmed.ncbi.nlm.nih.gov

[Development of CDK4 & 6 Inhibitor Abemaciclib in Breast Cancer]. [2021]