ARV-471 + Palbociclib for Breast Cancer

(mBC Trial)

Not currently recruiting at 20 trial locations

Overseen By Arvinas Estrogen Receptor, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Arvinas Inc.

Must be taking: CDK4/6 inhibitors

Must not be taking: High-dose corticosteroids

Disqualifiers: Symptomatic brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with a specific type of advanced breast cancer that resists standard treatments. Researchers examine the safety and effectiveness of ARV-471 (Vepdegestrant) alone and in combination with palbociclib (IBRANCE®) to evaluate their impact on tumors. The trial targets women with estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have previously undergone hormone therapy and chemotherapy. Participants should be postmenopausal and have tried certain therapies without success. 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 treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking any prior anti-cancer or investigational therapy at least 14 days before starting the study drug. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

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

Research has shown that ARV-471, also known as vepdegestrant, is generally safe for patients with advanced breast cancer. Studies indicate that patients taking ARV-471 alone have not reported any major safety issues, and it was well-tolerated even by those who had undergone previous cancer treatments.

When combined with palbociclib, a medication already approved by the FDA for breast cancer, ARV-471 remains safe. Data shows that this combination has been tested in patients with advanced breast cancer and continues to be safe and effective. Patients in these studies experienced manageable side effects, with no unexpected or severe problems.

Overall, both ARV-471 alone and with palbociclib appear to be safe options based on current studies. However, as with any treatment, discussing potential risks and benefits with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ARV-471 and palbociclib for breast cancer because these treatments offer a novel approach. Unlike standard therapies that often focus on hormone receptor blocking, ARV-471 is a selective estrogen receptor degrader (SERD), which means it not only blocks but also degrades estrogen receptors, potentially leading to more effective tumor suppression. Palbociclib, on the other hand, is a CDK4/6 inhibitor that helps prevent cancer cell division. This combination aims to tackle cancer growth from two fronts, offering a promising new strategy for patients with hormone receptor-positive breast cancer.

What evidence suggests that ARV-471 and palbociclib could be effective for breast cancer?

Research has shown that ARV-471, also known as Vepdegestrant, holds promise for treating certain types of breast cancer. In a previous study, it helped shrink or slow tumor growth in 38% of patients. ARV-471 also reduces over 90% of estrogen receptors in cancer cells, which can help stop these cells from multiplying.

In this trial, some participants will receive ARV-471 alone, while others will receive it in combination with palbociclib. When combined with palbociclib, ARV-471 remains effective. This combination helped patients with advanced breast cancer live for an average of 13.9 months without their cancer worsening. Palbociclib alone has been shown to lower the risk of cancer progression by about 30% when used with other treatments. These findings suggest that ARV-471, both alone and with palbociclib, could be effective options for this type of breast cancer. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with ER+/HER2- advanced breast cancer who've had prior hormonal therapy and chemotherapy. They must have measurable disease, be over 18, willing to undergo biopsies, and can't have more than two prior chemo regimens for advanced disease or symptomatic brain metastases.

Inclusion Criteria

I have been treated with hormone therapy for my advanced cancer for at least 6 months.

My cancer's size or presence can be measured by scans done within the last 28 days.

I have had 2 or fewer chemotherapy treatments for my advanced disease.

Exclusion Criteria

I haven't had radiation that affected more than 25% of my bone marrow or any in the last 4 weeks, except for pain relief.

I haven't taken any cancer treatment or experimental drugs in the last 14 days.

I have brain metastases but am stable and off high-dose steroids for 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ARV-471 alone or in combination with palbociclib in 28-day cycles to assess safety, tolerability, and anti-tumor activity

up to 2 years

Monthly visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• ARV-471
• Palbociclib (IBRANCE®)

Trial Overview The study tests ARV-471's safety and effectiveness alone and with palbociclib in treating breast cancer that has spread or cannot be cured by standard treatments. It involves increasing doses to find the right amount and then expanding the group to further assess its effects.

How Is the Trial Designed?

Group I: ARV-471 and palbociclib (IBRANCE®) Experimental Treatment 1 Intervention

Part C: Daily oral dosages of ARV-471 for 28 days in combination with palbociclib (IBRANCE®) for 21 days.

Group II: ARV-471 Experimental Treatment 1 Intervention

Parts A and B: ARV-471 administered QD or BID for 28 day cycles.

ARV-471 is already approved in United States for the following indications:

Approved in United States as Vepdegestrant for:

• None approved; under investigation for ER+/HER2- metastatic breast cancer

Who Is Running the Clinical Trial?

Arvinas Inc.

Lead Sponsor

Trials

4

Recruited

730+

Arvinas Estrogen Receptor, Inc.

Lead Sponsor

Trials

19

Recruited

2,400+

Pfizer

Industry 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

Citations

1. ir.arvinas.com ir.arvinas.com/news-releases/news-release-details/arvinas-announces-arv-471-achieves-clinical-benefit-rate-38

Arvinas Announces ARV-471 Achieves a Clinical Benefit ... In the VERITAC trial, ARV-471 shows a favorable tolerability profile and demonstrates a clinical benefit rate of 38% (total n=71) (CBR: rate of ...

2. pfizer.com pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizers-vepdegestrant-significantly-improves

Arvinas and Pfizer's Vepdegestrant Significantly Improves ... Pivotal Phase 3 VERITAC-2 clinical trial results presented at ASCO demonstrate 2.9-month improvement in median progression-free survival ...

3. arvinasmedical.com arvinasmedical.com/wp-content/uploads/2022/06/Teh-AACR-2023-2.pdf

Enhanced Efficacy of Vepdegestrant (ARV-471), a Novel ... ARV-471 demonstrates superior ER degradation and antitumor activity compared to fulvestrant in endocrine sensitive and resistant xenograft models (1,2) and has ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38819400/

Oral Estrogen Receptor PROTAC Vepdegestrant (ARV-471 ... Results: Vepdegestrant induced ≥90% degradation of wild-type and mutant ER, inhibited ER-dependent breast cancer cell line proliferation in ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05463952

NCT05463952 | A Study to Learn About the Vepdegestrant ... The purpose of this clinical trial is to learn about the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ARV-471 as monotherapy in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11700046/

Safety and pharmacokinetics of vepdegestrant in Japanese ... Vepdegestrant 200 mg QD was well tolerated in Japanese patients with ER+/HER2- advanced breast cancer with no notable differences in pharmacokinetics from ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39072356/

VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ... In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients with ER+/HER2- advanced breast ...