PF-07220060 + Letrozole for Breast Cancer

No longer recruiting at 67 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Pfizer

Must be taking: Letrozole

Must not be taking: Hormone replacement therapy

Disqualifiers: Myocardial infarction, Angina, Heart failure, others

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

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new medicine, PF-07220060 (Atirmociclib), combined with letrozole, compared to letrozole alone, for treating a specific type of breast cancer. The focus is on postmenopausal women with hormone receptor-positive (HR+), HER2-negative breast cancer who have not received prior treatment. Participants will be randomly assigned to receive either the combination of PF-07220060 and letrozole or letrozole alone, both administered as tablets. The study includes a screening period, a 14-day treatment phase, and at least one biopsy to examine cancer cells. Regular safety checks, such as blood tests and interviews, will occur throughout the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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.

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

Research shows that combining PF-07220060 and letrozole may help treat breast cancer. Earlier studies have demonstrated activity against tumors in patients with hormone receptor-positive, HER2-negative breast cancer. This finding suggests the treatment might effectively target cancer cells.

PF-07220060 is still under investigation, so its full safety profile remains unknown. However, earlier studies did not identify any major safety issues. Since this study is in Phase 2, the treatment has already passed initial safety tests and is now being tested on more people to assess tolerability.

Letrozole is a well-known drug already used to treat breast cancer, with a well-established safety profile, and most patients tolerate it well.

Participants in this trial will undergo regular safety checks, including blood tests and meetings with study staff, to monitor for any side effects. ^{1 2 3 4 5}

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

Researchers are excited about PF-07220060 combined with letrozole for breast cancer because it offers a new approach to treatment. Unlike standard therapies that primarily target hormone receptors, PF-07220060 is notable for its unique mechanism of action, which potentially enhances the effectiveness of letrozole, a commonly used aromatase inhibitor. This combination could provide a more robust blockade against cancer cell growth. Additionally, the dual use of PF-07220060 and letrozole may offer benefits in terms of reducing resistance to treatment, a significant hurdle with current options.

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

This trial will compare the effectiveness of PF-07220060 plus letrozole with letrozole alone for treating hormone receptor-positive, HER2-negative breast cancer. Research has shown that combining PF-07220060 with letrozole may be effective. Specifically, earlier studies demonstrated a 58.8% overall response rate, with 94.1% of patients experiencing tumor shrinkage or halted cancer growth. PF-07220060 targets a protein called CDK4, which is involved in cell growth, potentially slowing down the cancer. These findings suggest that adding PF-07220060 to letrozole could enhance the treatment's effectiveness compared to using letrozole alone. ^{1 3 4 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 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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Letrozole
• PF-07220060

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Femara for:

• Breast cancer in postmenopausal women
• Increasing the chance of ovulation in women with polycystic ovary syndrome

Approved in European Union as Letrozole for:

• Early breast cancer in postmenopausal women
• Advanced breast cancer in postmenopausal women

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

Published Research Related to This Trial

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 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 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 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]

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]

Citations

1. 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 ... Atirmociclib combined with letrozole showed a 58.8% overall response rate and 94.1% clinical benefit rate in HR-positive, HER2-negative ...

2. 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 ...

3. 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 ...

4. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)01863-0/fulltext

520P Long-term safety and efficacy of first-line atirmociclib ... We present long-term safety and efficacy data assessing first-line (1L) ATI + letrozole (LET) in patients (pts) with HR+/HER2− metastatic breast cancer (mBC) ( ...

5. 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.

6. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/NCT06465368

Atirmociclib (PF-07220060) Atirmociclib | PF-07220060 is an investigational compound. Its safety and efficacy have not been established. AN INTERVENTIONAL, OPEN-LABEL, RANDOMIZED, ...

7. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/NCT06760637

Atirmociclib (PF-07220060) Atirmociclib (PF-07220060). Atirmociclib | PF-07220060 is an investigational compound. Its safety and efficacy have not been established.