PF-07220060 + Letrozole for Breast Cancer

Recruiting at27 trial locations

Age: 18+

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Pfizer

Must be taking: Letrozole

Must not be taking: Hormone replacement therapy

Disqualifiers: Myocardial infarction, Angina, Heart failure, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the effects of the study medicine PF-07220060 plus letrozole, compared with the effects of taking letrozole alone without PF-07220060 for treatment of breast cancer. This study is seeking for participants who are: * women of age 18 years and older post menopause (either naturally or surgically). * confirmed to have Hormone receptor (HR) positive, Human epidermal growth factor receptor 2 (HER2) negative breast cancer. HER2 negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2 negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface. * not been treated for their cancer before this study. Participants will be randomly assigned (like flipping a coin) to receive the treatment (PF-07220060 plus letrozole) or letrozole alone. Both PF-07220060 and letrozole are taken by mouth. PF-07220060 will be taken twice a day for 14 days. Letrozole will be taken once a day for 14 days. Participants will have a screening period for up to 28 days. If deemed fit, they will receive study treatment for 14 days, and then will have a follow-up visit about 28 days after their last dose. All participants will have at least one biopsy during the study. Biopsy is the removal of cells or tissues for examining. All participants will have a biopsy on Day 14. Additional assessments for safety including blood draws and interviews done by the site staff will be completed during the study.

Do I need to stop my current medications to join the trial?

The trial requires that you have not had any prior treatment for breast cancer, including chemotherapy, hormonal therapy, radiation, or surgery. You also cannot have used hormone replacement therapy or any estrogen-containing medication within 2 weeks before joining the study.

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

Research shows that combining a drug similar to PF-07220060, called palbociclib, with letrozole significantly improves progression-free survival (the time during which the cancer does not get worse) in patients with a specific type of advanced breast cancer. Letrozole alone is also effective in treating hormone-responsive early breast cancer in postmenopausal women. ^{1 2 3 4 5}

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

The combination of palbociclib (a drug similar to PF-07220060) and 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 used in treating advanced breast cancer and has an acceptable safety profile. ^{4 5 6 7 8}

How is the drug PF-07220060 + Letrozole unique for breast cancer treatment?

PF-07220060 combined with Letrozole is unique because it involves a novel drug, Atirmociclib, which may offer a different mechanism of action compared to existing treatments like Palbociclib plus Letrozole, which have been shown to significantly prolong progression-free survival in estrogen receptor-positive, HER2-negative advanced breast cancer. ^{1 3 4 7 9}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for postmenopausal women aged 18 or older with a specific type of untreated breast cancer that's HR positive and HER2 negative. They must not have had prior systemic therapy, radiation, surgery, or certain medications recently. Participants need to be able to undergo biopsies and have an ECOG performance status of 0 or 1.

Inclusion Criteria

I am a postmenopausal woman with HR-positive, HER2-negative breast cancer.

I agree to have two biopsies and can care for myself with minimal assistance.

My breast cancer has a Ki-67 score of 10% or higher and is in stages T1c to T4c, N0 to N2, M0.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Treatment

Participants receive PF-07220060 plus letrozole or letrozole alone for 14 days

2 weeks

Daily medication administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Letrozole (Hormone Therapy)
• PF-07220060 (Monoclonal Antibodies)

Trial Overview The study compares the effects of PF-07220060 combined with letrozole versus letrozole alone in treating breast cancer. Women will be randomly assigned to one of these treatments; both are oral medications taken for a period of 14 days followed by assessments.

Participant Groups

Group I: Arm A/Experimental/PF-07220060 plus letrozole Experimental Treatment 2 Interventions

PF-07220060 given as tablet by mouth twice a day for 14 days. Letrozole given as tablet by mouth once a day for 14 days.

Group II: Arm B/Control/letrozole Active Control 1 Intervention

Letrozole given by mouth once a day for 14 days.

Letrozole is already approved in Canada for the following indications:

Approved in Canada as Letrozole for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

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 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 more effective than tamoxifen for adjuvant therapy in postmenopausal women with hormone-responsive early breast cancer, and it is well tolerated by patients.

Extended therapy with letrozole after tamoxifen treatment is more effective than placebo, making it a valuable treatment option while ongoing trials investigate the best duration and comparison with other aromatase inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. Keating, GM.[2021]

In the PALOMA-2 trial, palbociclib combined with letrozole significantly improved progression-free survival (PFS) in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer, with a median PFS of 37.2 months compared to 27.4 months for the placebo group.

The study found that 44% of patients on palbociclib achieved an objective response, and even those who did not achieve a response still experienced a significant prolongation of PFS, indicating that palbociclib + letrozole offers substantial clinical benefits regardless of the response status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2. Rugo, HS., Finn, RS., Gelmon, K., et al.[2021]

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]

Ribociclib combined with letrozole is more cost-effective than palbociclib combined with letrozole, saving $43,037 while providing an additional 0.086 quality-adjusted life-years (QALYs).

When compared to letrozole alone, ribociclib plus letrozole has an incremental cost-effectiveness ratio of $210,369 per QALY, making it a viable option for postmenopausal women with advanced breast cancer at higher willingness-to-pay thresholds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective. Mistry, R., May, JR., Suri, G., et al.[2023]

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 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 phase II PALOMA-1/TRIO-18 trial involving 165 postmenopausal women with advanced ER-positive, HER2-negative breast cancer, palbociclib combined with letrozole significantly improved progression-free survival (PFS) to 20.2 months compared to 10.2 months with letrozole alone, indicating its efficacy as a first-line treatment.

While Grade 3-4 neutropenia was the most common adverse event associated with the palbociclib and letrozole combination, the incidence of neutropenia decreased over time, and most patients did not experience severe infections, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. Finn, RS., Crown, JP., Ettl, J., et al.[2022]

In a study of 666 postmenopausal women with advanced breast cancer, Asian patients receiving palbociclib plus letrozole experienced a significantly longer progression-free survival (PFS) of 25.7 months compared to 13.9 months for those on placebo plus letrozole, indicating the efficacy of this combination treatment.

While hematologic toxicities like neutropenia were more common in Asian patients, they were manageable, and quality of life remained stable, suggesting that palbociclib plus letrozole is a safe and effective treatment option for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. Im, SA., Mukai, H., Park, IH., et al.[2023]

References

1. 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]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer. [2021]

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

Progression-free Survival Outcome Is Independent of Objective Response in Patients With Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative Advanced Breast Cancer Treated With Palbociclib Plus Letrozole Compared With Letrozole: Analysis From PALOMA-2. [2021]

4. 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]

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

Cost-Effectiveness of Ribociclib plus Letrozole Versus Palbociclib plus Letrozole and Letrozole Monotherapy in the First-Line Treatment of Postmenopausal Women with HR+/HER2- Advanced or Metastatic Breast Cancer: A U.S. Payer Perspective. [2023]

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

Palbociclib and Letrozole in Advanced Breast Cancer. [2022]

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

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18. [2022]

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

Palbociclib Plus Letrozole as First-Line Therapy in Postmenopausal Asian Women With Metastatic Breast Cancer: Results From the Phase III, Randomized PALOMA-2 Study. [2023]