ARV-471 + Palbociclib for Advanced Breast Cancer

(VERITAC-3 Trial)

Not currently recruiting at 46 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: CDK4/6 inhibitors, SERDs

Disqualifiers: Cardiovascular diseases, Liver function, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new medicine, ARV-471 (an experimental treatment), combined with palbociclib for advanced breast cancer. The researchers aim to assess the safety and effectiveness of this combination compared to the current standard treatment, letrozole plus palbociclib. Participants should have breast cancer that has spread or cannot be fully treated with surgery or radiation and should not have received medications like tamoxifen or letrozole for advanced disease. The trial involves taking oral medications daily and requires visits to the study clinic approximately once every four weeks. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to the development of a promising new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those currently using or needing strong CYP3A4 inhibitors or inducers (substances that affect how drugs are processed in the body). 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 shows that ARV-471, when combined with palbociclib, appears safe. In earlier studies, researchers tested ARV-471 both alone and with palbociclib. These studies found that patients generally tolerated ARV-471 well, even those with extensive prior treatments. Some side effects occurred, but they were usually mild for most participants. This suggests that using ARV-471 with palbociclib might safely treat advanced breast cancer.

Palbociclib is already a common breast cancer treatment, widely used and considered safe for many patients. The trial aims to determine if adding ARV-471 to palbociclib provides additional benefits without causing serious side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer?

Researchers are excited about ARV-471 for advanced breast cancer because it represents a novel approach to treatment. Unlike standard therapies like Letrozole, which target hormone receptors indirectly, ARV-471 directly degrades estrogen receptors, potentially leading to a more effective reduction in cancer growth. This new mechanism of action offers hope for improved outcomes, especially for patients whose cancer has become resistant to traditional hormone therapies. Additionally, ARV-471 is taken orally once daily, providing a convenient treatment option that fits seamlessly into patients' daily routines.

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

Research has shown that ARV-471, when combined with palbociclib, may help treat advanced estrogen receptor-positive breast cancer. In this trial, participants in the investigational arm will receive this combination. Studies have found that it can remain effective in patients who have already undergone treatment for this cancer type. Additionally, lab tests demonstrated that ARV-471 with palbociclib slowed tumor growth more effectively than palbociclib with other treatments. These findings suggest that ARV-471 could be a promising option for slowing or stopping cancer growth. ^{1 2 5 6 7}

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 adults with advanced breast cancer that can't be cured by surgery or radiation, who haven't had systemic treatment for their recurrent or metastatic disease. They should have estrogen receptor positive and HER2 negative tumors, good performance status (ECOG 0-2), and be able to provide tissue samples.

Inclusion Criteria

Phase 3 only: Participants should be willing to provide blood and tumor tissue

I haven't had systemic treatment for my cancer that has returned or spread.

My breast cancer is ER positive and HER2 negative.

Exclusion Criteria

My liver, kidneys, and bone marrow are not working well.

I cannot take pills normally due to severe nausea, vomiting, or certain stomach/intestinal surgeries.

I have heart problems or significant heart disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Study Lead-in (SLI)

Participants are randomly assigned to one of two dose levels of palbociclib in combination with ARV-471 to determine the recommended Phase 3 dose

4 cycles (each cycle is 28 days)

Visits every 4 weeks

Phase 3 Treatment

Participants receive either ARV-471 plus palbociclib or letrozole plus palbociclib until disease progression or unacceptable toxicity

Up to approximately 4 years

Visits every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ARV-471 (PF-07850327)
• Letrozole
• Palbociclib

Trial Overview The study tests ARV-471 combined with palbociclib against the standard letrozole plus palbociclib in treating advanced breast cancer. Initially, two doses of palbociclib are tested to find the best one for Phase 3, where participants will randomly receive either combination orally once daily until progression or unacceptable side effects.

How Is the Trial Designed?

Group I: Arm A (Investigational Arm) Experimental Treatment 2 Interventions

Participants will receive: * ARV-471, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle

Group II: Arm B (Comparator Arm): Active Control 2 Interventions

Participants will receive: * Letrozole, orally, once daily, continuously, in a 28-day cycle, plus * Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.

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

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

In a phase 3 study involving 666 postmenopausal women with ER-positive, HER2-negative advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival to 24.8 months compared to 14.5 months with letrozole alone, indicating its efficacy as a treatment option.

While palbociclib plus letrozole showed better outcomes, it also resulted in higher rates of serious side effects, such as neutropenia (66.4% vs. 1.4% in the placebo group), highlighting the need for careful monitoring of patients during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib and Letrozole in Advanced Breast Cancer. Finn, RS., Martin, M., Rugo, HS., et al.[2022]

In the PALOMA-2 trial involving 666 postmenopausal women with ER+/HER2- advanced breast cancer, the combination of palbociclib and letrozole significantly improved progression-free survival compared to letrozole alone, with a hazard ratio of 0.58.

Neutropenia was the most common adverse event associated with palbociclib, occurring in 95.3% of patients, but it was mostly manageable through dose modifications and did not compromise treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Diéras, V., Harbeck, N., Joy, AA., et al.[2020]

In a study with a median follow-up of about 38 months, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in women with advanced estrogen receptor-positive (ER+)/HER2-negative breast cancer, with a median PFS of 27.6 months compared to 14.5 months for the placebo group.

The treatment not only prolonged PFS but also delayed the need for chemotherapy and maintained a favorable safety profile and quality of life for patients, suggesting that palbociclib-letrozole should be the standard first-line therapy for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib plus letrozole as first-line therapy in estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with extended follow-up. Rugo, HS., Finn, RS., Diéras, V., et al.[2023]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

In the PALOMA-2 trial, palbociclib combined with letrozole significantly prolonged progression-free survival (PFS) in postmenopausal patients with advanced breast cancer, regardless of preexisting health conditions.

The safety profile of palbociclib plus letrozole was consistent across different preexisting conditions, with similar rates of treatment-emergent adverse events and dose modifications, indicating it is a safe option for patients with various health backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer with preexisting conditions: A post hoc analysis of PALOMA-2. Gelmon, K., Walshe, JM., Mahtani, R., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05909397

NCT05909397 | A Study of Vepdegestrant (ARV-471, PF- ... The purpose of this study is to understand the safety and effects of the study medicine ARV-471 (PF-07850327) given together with palbociclib in advanced ...

2. onclive.com onclive.com/view/vepdegestrant-plus-palbociclib-sustains-efficacy-in-advanced-er-breast-cancer

Vepdegestrant Plus Palbociclib Sustains Efficacy in ... Vepdegestrant plus palbociclib maintained clinical efficacy and safety in patients with pretreated, advanced ER-positive, HER2-negative breast cancer.

3. humanforschung-schweiz.ch humanforschung-schweiz.ch/en/trial-search/study-detail/63742/translate/en/?cHash=b5cb8f73990a7337b847bfb104352f0d

Randomized, open Phase III study of ARV-471 (PF ... Randomized, open Phase III study of ARV-471 (PF-07850327) plus Palbociclib compared to Letrozole plus Palbociclib in patients with advanced ER(+)/HER2(-) breast ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS1120

ARV-471, an estrogen receptor (ER) PROTAC degrader ... ARV-471 plus palbociclib resulted in substantially greater tumor growth inhibition in xenograft models compared with palbociclib plus ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04072952

NCT04072952 | A Phase 1/2 Trial of ARV-471 Alone and in ... A Phase 1/​2 Trial of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With ER+/​HER2- Locally Advanced or Metastatic Breast Cancer (mBC).

6. asco.org asco.org/abstracts-presentations/ABSTRACT371436

ARV-471, an estrogen receptor (ER) PROTAC degrader ... Here we describe Part C of the phase 1/2 study, which evaluates the safety and clinical activity of ARV-471 plus palbociclib in patients with breast cancer who ...

7. 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 ... ARV-471 continues to show activity in heavily pre-treated patients with locally advanced or metastatic ER+/HER2- breast cancer.