ARV-471 + Abemaciclib for Advanced Breast Cancer

Not currently recruiting at 54 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of a new treatment combination for advanced or metastatic breast cancer. Participants will take two oral medications, ARV-471 (a potential new drug) and abemaciclib, to determine if they work together to treat breast cancer that has spread and no longer responds to standard treatments. This study targets individuals with hormone-sensitive (estrogen receptor positive) breast cancer that cannot be fully treated with surgery or radiation. Eligible participants will have tried one or two previous treatments for advanced cancer and will continue the new treatment as long as it remains effective. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

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

Research has shown that combining ARV-471 with abemaciclib appears safe and effective. In previous studies, 62.5% of patients experienced some benefit, and 26.7% had a positive response to this treatment combination, indicating that many patients tolerate it well.

The FDA has already approved abemaciclib for other uses, so its side effects are well-known and manageable by doctors. However, ARV-471 is still under study, and not all its side effects are known. As this trial is in the early stages, researchers are still learning about the treatment's safety. Participants will have regular check-ups to monitor their bodies' reactions to the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ARV-471 combined with Abemaciclib because it introduces a novel approach to treating advanced breast cancer. While traditional treatments often rely on hormone therapies or chemotherapy, ARV-471 is a selective estrogen receptor degrader (SERD), which targets and breaks down estrogen receptors that fuel cancer growth. This combination with Abemaciclib, a CDK4/6 inhibitor, aims to more effectively halt cancer cell proliferation. Together, these drugs offer a promising new strategy that could potentially overcome resistance seen with current hormone therapies.

What evidence suggests that ARV-471 and Abemaciclib might be an effective treatment for advanced breast cancer?

Research has shown that abemaciclib effectively treats advanced breast cancer. Studies have found it benefits patients with hormone receptor-positive breast cancer who haven't responded to other treatments. ARV-471, a newer drug, targets estrogen receptors, which often contribute to breast cancer growth. Early research suggests that combining ARV-471 with abemaciclib, as tested in this trial, might enhance treatment effectiveness. This combination could provide a new option for those with advanced breast cancer unresponsive to other therapies. ^{2 6 7 8 9}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2017/208716Orig1s000MultidisciplineR.pdf

208716Orig1s000 - accessdata.fda.gov observed with other cancer cell lines, the sensitivity of breast cancer cell lines to abemaciclib ... advanced breast cancer: Results from the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524203/

VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER ... The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05169567

Study Details | NCT05169567 | Abemaciclib (LY2835219) ... This study will evaluate the effect of adding abemaciclib to fulvestrant for the treatment of hormone receptor-positive (HR+), human epidermal growth factor ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601721/

Pharmacoeconomic Review - Abemaciclib (Verzenio) - NCBI A cost-effectiveness analysis of abemaciclib in the treatment of advanced breast cancer in the MONARCH 3 indication: Canadian pCODR technical report ...

5. ir.arvinas.com ir.arvinas.com/news-releases/news-release-details/arvinas-and-pfizer-announce-positive-topline-results-phase-3

Press Release Details Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05548127

NCT05548127 | TACTIVE-U: A Study to Learn About the ... 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.

7. arvinasmedical.com arvinasmedical.com/development-program/vepdegestrant-arv-471-2/

Vepdegestrant ARV-471 Vepdegestrant is currently under investigation. Its safety and efficacy have not been established. Vepdegestrant is being co-developed with Pfizer.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05654623

NCT05654623 | A Study to Learn About a New Medicine ... The purpose of this study is to learn about the safety and effects of the study medicine ARV-471 (PF-07850327, vepdegestrant) compared to fulvestrant (FUL)

9. pfizer.com pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-initial-phase-1b-data-tactive-u

Arvinas and Pfizer Announce Initial Phase 1b Data from the ... Vepdegestrant in combination with abemaciclib demonstrated encouraging clinical activity (clinical benefit rate: 62.5%; overall response rate: 26.7%)