ARV-471 + Palbociclib for Advanced Breast Cancer

(VERITAC-3 Trial)

Recruiting at 41 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

59 Participants Needed

Trial Summary

What is the purpose of this trial?

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 breast cancer. In particular, the study will compare the combination of ARV-471 plus palbociclib to standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines already used for treatment of breast cancer. ARV-471 is a new medicine under study. This study is seeking participants who have breast cancer that: * Have a locally advanced or metastatic disease and cannot be fully cured by surgery or radiation therapy. A metastatic disease is when disease has spread to other parts of the body. * Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor positive disease. * Have not received any prior medicine for advanced disease. Example medications include tamoxifen or letrozole or exemestane. The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial. During SLI, two dose levels of palbociclib in combination with ARV-471 will be explored in parallel. Assignment to the palbociclib dose is by chance. Half of the participant will receive one dose and the other half another palbociclib dose. The purpose of SLI is to determine the recommended Phase 3 dose of palbociclib to be administered in combination with ARV-471. In the Phase 3, half of the participants will take ARV-471 plus palbociclib while the other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take the study medicines by mouth, with food, once a day. Participants will take the study medicines until breast cancer increase in size or side effects become too severe. Side effects refer to unwanted reactions to medications. Participants will visit the study clinic about once every 4 weeks.

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.

What data supports the effectiveness of the drug ARV-471 + Palbociclib for advanced breast cancer?

Palbociclib, when used with letrozole, has been shown to significantly extend the time patients live without their cancer getting worse in women with a specific type of advanced breast cancer. This combination has been approved by the FDA and has demonstrated a large improvement in delaying cancer progression compared to letrozole alone. ^{1 2 3 4 5}

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

Palbociclib, when used with letrozole, has been shown to be generally safe in humans, with the most common side effect being neutropenia (a low level of white blood cells). This combination has been studied in women with advanced breast cancer and has an acceptable safety profile. ^{1 2 4 6 7}

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

The combination of ARV-471, a novel estrogen receptor degrader, with Palbociclib, a CDK4/6 inhibitor, offers a unique approach by targeting both estrogen receptors and cell cycle regulation, potentially enhancing treatment effectiveness for advanced breast cancer compared to existing therapies that typically focus on one mechanism. ^{1 2 3 4 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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 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]

References

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

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. [2022]

2. France pubmed.ncbi.nlm.nih.gov

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

3. Netherlands 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. [2023]

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

Palbociclib and Letrozole in Advanced Breast Cancer. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. [2017]

6. England 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. [2020]

7. Netherlands 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. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Letrozole and palbociclib versus chemotherapy as neoadjuvant therapy of high-risk luminal breast cancer. [2020]