PF-07220060 + Letrozole for Breast Cancer

(FourLight-3 Trial)

Recruiting at 158 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

Trial Summary

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.

What data supports the effectiveness of the drug PF-07220060 + Letrozole for breast cancer?

Letrozole, a component of the treatment, has been shown to effectively shrink tumors and improve disease-free survival in postmenopausal women with hormone-sensitive breast cancer. It is also more effective and has lower toxicity compared to tamoxifen, another breast cancer treatment. ^{1 2 3 4 5}

Is the combination of PF-07220060 and Letrozole safe for humans?

Letrozole is generally well-tolerated, with common side effects including hot flushes, joint pain, and a higher risk of bone fractures. It has been used safely in breast cancer treatment, but specific safety data for PF-07220060 is not provided in the available research. ^{1 3 6 7 8}

What makes the drug PF-07220060 + Letrozole unique for breast cancer treatment?

The combination of PF-07220060 with Letrozole is unique because it potentially offers a novel approach by combining a new investigational drug (PF-07220060) with Letrozole, a well-established aromatase inhibitor that reduces estrogen levels, which is crucial for treating hormone-sensitive breast cancer in postmenopausal women. This combination may enhance the effectiveness of Letrozole by targeting different pathways involved in cancer growth. ^{1 3 9 10 11}

What is the purpose of this trial?

The purpose of this study is to determine the safety and efficacy of PF-07220060 with letrozole compared to approved treatments (ie, palbociclib, ribociclib or abemaciclib with letrozole) in people with breast cancer: * HR-positive (breast cancer cells that need estrogen or progesterone to grow) * HER2-negative (cells that have a small amount or none of a protein called HER2 on their surface); * locally advanced (that has spread from where it started to nearby tissue or lymph nodes) or metastatic disease (the spread of cancer to other places in the body) * who have not received any prior systemic anti-cancer treatment for advanced/metastatic disease. Approximately half of the participants will receive PF-07220060 plus letrozole while the other half of participants will receive the investigator's choice of treatment plus letrozole. The study team will monitor how each participant is doing with the study treatment during regular visits at the study clinic.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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 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]

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]

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]

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]

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, 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]

References

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

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

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

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022]

3. Spain pubmed.ncbi.nlm.nih.gov

The role of letrozole (Femara(R)) in breast cancer therapy: A clinical review. [2019]

4. 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]

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

Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized double-blind multicenter study. [2022]

6. 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]

7. England 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. [2021]

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

Letrozole: advancing hormone therapy in breast cancer. [2018]

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

Approval summary: letrozole in the treatment of postmenopausal women with advanced breast cancer. [2018]

10. United States 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. [2022]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Letrozole as primary medical therapy for locally advanced and large operable breast cancer. [2022]