PF-07220060 + Letrozole for Breast Cancer

(FourLight-3 Trial)

Recruiting at 489 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Letrozole

Disqualifiers: Visceral crisis, CNS metastases, 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: Unknown

Duration: Up to 4 years

1020 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for breast cancer that requires hormones to grow (HR-positive) and has a low level of a specific protein (HER2-negative). It targets cancers that have spread to nearby tissues or other parts of the body and have not yet received systemic therapies. Participants will receive either the new treatment, PF-07220060 (an experimental treatment) with letrozole, or a standard treatment with letrozole. Individuals with breast cancer meeting these specific conditions, who have not undergone prior treatments for their advanced disease, are suitable candidates for this trial. The trial will regularly monitor participants to assess treatment effectiveness. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that participants should not have received any prior systemic anti-cancer treatment for advanced or metastatic disease.

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

Research has shown that combining PF-07220060 and letrozole is generally well-tolerated by patients with HR-positive, HER2-negative metastatic breast cancer. Some patients experienced side effects like neutropenia, but these were common and manageable. The treatment also demonstrated promising efficacy.

Letrozole, often used with other breast cancer treatments, is usually well-tolerated. Common side effects include tiredness, hot flashes, and joint pain, which are generally mild and manageable.

This trial is in a later phase, indicating that earlier studies have provided evidence of the treatment's safety. This is encouraging for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about PF-07220060 for breast cancer because it represents a new approach in targeting the disease. Unlike standard treatments, which often involve CDK4/6 inhibitors like palbociclib, PF-07220060 has a unique mechanism that might offer a different way to disrupt cancer cell growth. In combination with letrozole, a common hormone therapy, PF-07220060 could potentially enhance treatment effectiveness and offer new hope for patients who may not respond well to current options.

What evidence suggests that PF-07220060 with letrozole might be an effective treatment for breast cancer?

Research has shown that using PF-07220060 with letrozole, which participants in Arm A of this trial may receive, may effectively treat HR-positive, HER2-negative metastatic breast cancer. Studies have found that this combination can help shrink tumors or halt their growth. Early results indicated that patients responded well to this treatment, even after trying other treatments. Additionally, the treatment was generally safe, with few serious side effects. Overall, this could be a promising option for individuals with this type of breast cancer. ^{6 7 8 9 10}

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 HR-positive, HER2-negative breast cancer that's locally advanced or metastatic. They should not have had any prior systemic anti-cancer treatments for their advanced condition.

Inclusion Criteria

Measurable disease or non-measurable bone only disease as defined by RECIST version 1.1

My tumor is positive for estrogen or progesterone receptors.

My breast cancer is advanced and cannot be removed by surgery or cured with radiation.

Exclusion Criteria

I have or had cancer spread to my brain or spinal cord.

My cancer returned within 12 months after my last CDK4/6 inhibitor treatment.

In visceral crisis at risk of immediately life-threatening complications in the short term

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-07220060 plus letrozole or investigator's choice of CDK4/6 inhibitor plus letrozole

Up to 4 years

Regular visits at the study clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 13 years

What Are the Treatments Tested in This Trial?

Interventions

• PF-07220060

Trial Overview The study tests the safety and effectiveness of PF-07220060 combined with letrozole against approved treatments (palbociclib, ribociclib, or abemaciclib with letrozole). Participants are randomly chosen to receive either the new combination or standard treatment.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

PF-07220060 tablet taken by mouth plus Letrozole tablet taken by mouth

Group II: Arm B Active Control 4 Interventions

Investigator's Choice of CDK4/6 inhibitor (tablet/capsule) taken by mouth with letrozole tablet taken by mouth

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

Published Research Related to This Trial

Letrozole is an effective aromatase inhibitor for postmenopausal women with hormone-sensitive breast cancer, showing significant tumor reduction and well-tolerated at low daily doses, as confirmed by recent phase III clinical studies.

It has demonstrated superior efficacy and lower toxicity compared to tamoxifen in first-line therapy for advanced breast cancer, and is also a viable option for second-line treatment after tamoxifen failure, with potential benefits in early breast cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. Crucitta, E., Locopo, N., Silvestris, N., et al.[2019]

Letrozole has been fully approved by the FDA for treating postmenopausal women with hormone receptor-positive early breast cancer, showing a significant improvement in disease-free survival compared to tamoxifen, with a hazard ratio of 0.87 in the adjuvant trial.

While letrozole is effective, it is associated with a higher risk of bone fractures and myocardial infarction compared to tamoxifen, which has its own risks such as endometrial cancer and thromboembolic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval. Cohen, MH., Johnson, JR., Justice, R., et al.[2021]

In a study of 92 postmenopausal women with operable HR-positive/HER2-negative breast cancer, the combination of letrozole and lapatinib showed a clinical response rate of 70%, which is comparable to the 63% response rate seen with letrozole plus placebo, indicating that the combination therapy is feasible and has manageable side effects.

The presence of PIK3CA mutations significantly increased the likelihood of a clinical response to letrozole-lapatinib, with a response rate of 93% in patients with the mutation compared to 63% in those without, suggesting a potential biomarker for treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Double-blind, placebo-controlled, multicenter, randomized, phase IIb neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative, operable breast cancer. Guarneri, V., Generali, DG., Frassoldati, A., et al.[2022]

Letrozole, a type 2 aromatase inhibitor, effectively reduces estrogen levels in postmenopausal women, leading to improved disease-free survival in breast cancer patients compared to other treatments like tamoxifen.

The drug is generally well-tolerated, though it may cause side effects such as hot flushes, joint pain, and a potential increased risk of fractures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: advancing hormone therapy in breast cancer. Lee, RJ., Armstrong, AC., Wardley, AM.[2018]

In a study of 337 postmenopausal women with ER and/or PgR positive breast cancer, letrozole demonstrated a significantly higher overall objective response rate (55%) compared to tamoxifen (36%) after four months of treatment.

Letrozole also showed superior results in secondary endpoints, including ultrasound response (35% vs. 25%) and mammographic response (34% vs. 16%), while both treatments were well tolerated, indicating letrozole's effectiveness as a preoperative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. Eiermann, W., Paepke, S., Appfelstaedt, J., et al.[2022]

In a study of 150 breast cancer patients, those receiving sequential treatment with letrozole and tamoxifen showed a higher overall response rate and fewer adverse reactions compared to those on letrozole alone.

Both treatment methods resulted in similar survival rates, but the sequential therapy group had a significantly lower recurrence rate and better improvement in blood lipid levels, indicating a potentially better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. Lu, X., Qian, C.[2023]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[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]

Letrozole is an effective aromatase inhibitor that significantly reduces estrogen levels in postmenopausal women, achieving maximal suppression within 2-3 days and demonstrating a 75-95% decrease in plasma concentrations of estradiol and estrone.

In clinical trials, letrozole (2.5 mg) showed superior efficacy compared to tamoxifen in terms of time to progression and objective response rate in treating hormone receptor-positive or unknown locally advanced or metastatic breast cancer, leading to its FDA approval for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer. Cohen, MH., Johnson, JR., Li, N., et al.[2018]

Letrozole, at both 2.5 mg and 10 mg doses, was effective as a neoadjuvant therapy for locally advanced breast cancer, with significant reductions in tumor volume observed in all patients, allowing for breast-conserving surgery.

There were no significant differences in efficacy between the two doses, and both were well-tolerated with no recordable side effects, indicating a favorable safety profile for letrozole in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Dixon, JM., Love, CD., Bellamy, CO., et al.[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/NCT06760637

NCT06760637 | Study of PF-07220060 With Letrozole in ... The purpose of this study is to determine the safety and efficacy of PF-07220060 with letrozole compared to approved treatments.

2. onclive.com onclive.com/view/atirmociclib-plus-letrozole-demonstrates-preliminary-efficacy-and-safety-in-hr-her2-negative-metastatic-breast-cancer

Atirmociclib Plus Letrozole Demonstrates Preliminary ... Preliminary data showed atirmociclib plus letrozole yielded antitumor activity in HR-positive/HER2-negative metastatic breast cancer.

3. aacrjournals.org aacrjournals.org/clincancerres/article/31/12_Supplement/P5-07-28/752659/Abstract-P5-07-28-The-next-generation-CDK4

The next-generation CDK4-selective inhibitor atirmociclib (PF ... Here, we present the efficacy and safety results from an expansion cohort in the phase 1/2a study of atirmociclib in combination with letrozole ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3009

mBC who progressed on prior CDK4/6 inhibitors ... Results: At data cut off (Nov 1, 2022), 34 pts with advanced solid tumors received PF-07220060 in monotherapy dose escalation (Part 1A: 100–500 ...

5. esmoopen.com esmoopen.com/article/S2059-7029(24)00974-8/fulltext

184MO First-in-human phase I/IIa study of ... PF-07220060 + ET showed a favorable safety profile with few hematologic adverse events and infrequent dose modifications, and promising efficacy despite prior ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3108

First-in-human phase 1/2a study of the first-in-class, next- ... PF-07220060 + ET was well tolerated in pts with HR+/HER2− mBC across post-CDK4/6i and CDK4/6i-naïve cohorts. Incidence of G3 neutropenia and other TEAEs was ...

7. onclive.com onclive.com/view/novel-cdk4-inhibitor-shows-activity-and-safety-in-hr-her2-metastatic-breast-cancer

Novel CDK4 Inhibitor Shows Activity and Safety in HR+ ... PF-07220060 plus endocrine therapy was tolerable and generated robust response rates in HR-positive, HER2-negative metastatic breast cancer.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04557449

NCT04557449 | Study to Test the Safety and Tolerability of ... This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060

9. aacrjournals.org aacrjournals.org/cancerres/article/84/7_Supplement/ND12/742238/Abstract-ND12-Discovery-of-PF-07220060-a-potent

Abstract ND12: Discovery of PF-07220060, a potent and ... PF-07220060 was developed based on the clinical need to improve efficacy and safety outcomes in patients treated with currently approved dual CDK4/6 inhibitors.

10. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS1129

International phase 3 clinical trial evaluating PF-07220060 ... Background: Substantial improvement in survival outcomes has been achieved with cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine ...