PF-07220060 + Fulvestrant for Advanced Breast Cancer

Not currently recruiting at 297 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Must be taking: CDK4/6 inhibitors, NSAIs

Must not be taking: Chemotherapy, Everolimus

Disqualifiers: Visceral crisis, CNS metastases, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of a new medicine, PF-07220060 (Atirmociclib), combined with fulvestrant for treating advanced breast cancer, compared to other common treatments. It targets breast cancer that has spread and cannot be cured with standard treatment. Participants will either take the new medicine with fulvestrant or receive a treatment chosen by their doctor, which could be fulvestrant alone or combined with everolimus and exemestane. The trial seeks individuals with advanced breast cancer that is hormone receptor-positive and HER2-negative who have tried other treatments. The goal is to determine which approach best manages this challenging condition. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify exactly which medications you must stop, but it mentions that you cannot take certain medications that are not allowed by the study. This includes other anti-cancer therapies, endocrine therapies, growth factors, chronic systemic corticosteroids, and certain inhibitors and inducers. It's best to discuss your current medications with the study doctor to see if they are allowed.

Will I have to stop taking my current medications?

The trial protocol does not specify exactly which medications you must stop, but it mentions that you cannot take certain medications that are not allowed by the study. This includes other anti-cancer therapies, some endocrine therapies, and specific drugs like strong CYP3A4/5 or UGT2B7 inhibitors and inducers, among others.

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

Previous studies have shown promise in treating breast cancer with the combination of PF-07220060 and fulvestrant. Research indicates that most people tolerate this treatment well, experiencing few serious blood-related side effects. In earlier studies, most participants did not need to adjust their dose due to side effects, suggesting the treatment's safety for many patients. The combination also demonstrated good response rates in patients with HR-positive, HER2-negative metastatic breast cancer. While some side effects occur, they are usually manageable, and the treatment could be effective for some individuals. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of PF-07220060 and fulvestrant for advanced breast cancer because it offers a unique approach compared to standard treatments like hormone therapy or chemotherapy. Unlike most treatments that primarily focus on hormone suppression, PF-07220060 targets proteins involved in cancer cell growth, potentially stopping the cancer from advancing. This dual-action approach, combining a new oral tablet with an existing injectable hormone therapy, may improve effectiveness and offer new hope for patients with advanced stages of the disease.

What evidence suggests that this trial's treatments could be effective for advanced breast cancer?

Research has shown that PF-07220060, one of the treatments in this trial, may help treat HR-positive, HER2-negative metastatic breast cancer. In earlier studies, combining PF-07220060 with letrozole resulted in a 58.8% overall response rate, indicating that many patients' cancer either shrank or stopped growing. Additionally, 94.1% of patients experienced some positive effects from the treatment. This trial will test PF-07220060 in combination with fulvestrant, while another arm will involve the investigator's choice of therapy, either fulvestrant alone or everolimus with exemestane. This evidence suggests that PF-07220060 could benefit patients with advanced breast cancer. ^{1 5 6 7 8}

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 advanced or metastatic breast cancer that has worsened after prior treatment. Participants must have a tumor responsive to hormones, provide a tissue sample, and have an ECOG Performance Status of ≤2. They should not be candidates for surgery or radiation with curative intent and must have progressed during or after CDK4/6i treatment.

Inclusion Criteria

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

I can take care of myself but might not be able to do heavy physical work.

I can provide a sample of my tumor preserved in paraffin.

Exclusion Criteria

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

Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study

I do not have active brain metastases or related conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either PF-07220060 plus fulvestrant or the investigator's choice of therapy (fulvestrant alone or everolimus with exemestane)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PF-07220060

Trial Overview The study compares the effectiveness of PF-07220060 taken orally twice daily combined with fulvestrant injections versus standard treatments chosen by the doctor (fulvestrant alone or everolimus with exemestane). The goal is to determine if PF-07220060 plus fulvestrant is safe and more effective than other options.

How Is the Trial Designed?

Group I: Arm A Experimental Treatment 2 Interventions

PF-07220060 to be taken by mouth as a tablet in combination with fulvestrant (a solution for injection)

Group II: Arm B Active Control 3 Interventions

Investigator's choice of therapy of either: * Fulvestrant alone (a solution for injection), or * Everolimus in combination with exemestane, both a tablet to be 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

Fulvestrant, an estrogen receptor antagonist, shows promising efficacy in treating metastatic ER positive and HER2 positive breast cancer, even after patients have progressed on anti-HER2 therapies, with reported response durations of up to 38 months.

The treatment is associated with limited toxicity, making it a valuable option for patients with extensive metastases, including skin and brain, highlighting the need for further research to define its role in comprehensive breast cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical benefit of fulvestrant monotherapy in the multimodal treatment of hormone receptor and HER2 positive advanced breast cancer: a case series. Rusz, O., Kószó, R., Dobi, Á., et al.[2020]

Fulvestrant, a selective estrogen receptor downregulator, is effective in treating hormone-receptor-positive advanced breast cancer, both as a second-line therapy after other treatments and in previously untreated patients, expanding its use in various settings.

The introduction of targeted agents like mTOR and CDK 4/6 inhibitors has enhanced the efficacy of fulvestrant when used in combination, leading to new treatment options for patients with advanced breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant in advanced breast cancer: evidence to date and place in therapy. Boér, K.[2022]

Fulvestrant is an effective ER antagonist for treating advanced breast cancer in postmenopausal women, showing similar efficacy to anastrozole and tamoxifen, with no cross-resistance to other endocrine therapies.

It is well tolerated, with fewer side effects such as joint disorders and hot flushes compared to other treatments, making it a valuable option for hormone-sensitive breast cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant - a new treatment for postmenopausal women with hormone-sensitive advanced breast cancer. Possinger, K.[2019]

In the PALOMA-3 trial, Korean patients with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer treated with palbociclib plus fulvestrant experienced a significantly longer median progression-free survival (PFS) of 12.3 months compared to 5.4 months for those on placebo plus fulvestrant.

Palbociclib was generally safe, with neutropenia being the most common side effect, and it showed a confirmed objective response rate of 21.1% compared to 11.8% for the placebo group, indicating its efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Plus Fulvestrant in Korean Patients from PALOMA-3 With Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Kim, JH., Im, SA., Sim, SH., et al.[2021]

Palbociclib, in combination with letrozole, is FDA-approved for treating postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer, showing its efficacy as an initial therapy.

The combination of palbociclib with fulvestrant has been found to provide better outcomes than fulvestrant alone for patients who have previously progressed on endocrine therapy, highlighting its potential in advanced treatment scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. Lu, J.[2022]

In a study of 263 postmenopausal women with ER-positive advanced breast cancer, fulvestrant 500 mg demonstrated a median progression-free survival (PFS) of 10.6 months and a clinical benefit rate (CBR) of 56.5%, indicating its efficacy in a real-world setting after prior anti-estrogen therapy.

The treatment was well tolerated, with the most common side effects being injection site pain (10.3%) and musculoskeletal disorders (7.6%), aligning with safety profiles observed in previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice. Blancas, I., Fontanillas, M., Conde, V., et al.[2022]

In the FLIPPER trial, the combination of palbociclib and fulvestrant significantly improved progression-free survival (PFS) in postmenopausal women with HR+/HER2- advanced breast cancer compared to placebo and fulvestrant.

Patient-reported outcomes indicated that while global health status and quality of life (QoL) were maintained during treatment with palbociclib/fulvestrant, the time to deterioration in QoL was longer with placebo/fulvestrant, suggesting that palbociclib/fulvestrant is a beneficial treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant versus placebo plus fulvestrant in postmenopausal women with endocrine-sensitive hormone receptor-positive and HER2-negative advanced breast cancer: patient-reported outcomes from the FLIPPER trial. Tibau, A., Martínez, MT., Ramos, M., et al.[2023]

In the PALOMA-3 study involving 521 patients with hormone receptor-positive, HER2- metastatic breast cancer, the combination of palbociclib and fulvestrant significantly improved global quality of life (QoL) scores compared to fulvestrant plus placebo, indicating better patient-reported outcomes.

Patients receiving palbociclib plus fulvestrant also experienced a significant reduction in pain and a delay in deterioration of both global QoL and pain compared to those on fulvestrant alone, highlighting the efficacy of this combination therapy in managing symptoms and improving quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of life with palbociclib plus fulvestrant in previously treated hormone receptor-positive, HER2-negative metastatic breast cancer: patient-reported outcomes from the PALOMA-3 trial. Harbeck, N., Iyer, S., Turner, N., et al.[2022]

In a study involving 108 premenopausal women with advanced breast cancer, palbociclib combined with fulvestrant and goserelin significantly improved median progression-free survival (PFS) to 9.5 months compared to 5.6 months with placebo, indicating its efficacy in this population.

The treatment was well-tolerated, with common side effects including neutropenia and infections, but it did not interfere with ovarian suppression from goserelin, suggesting it could be a viable option to delay chemotherapy for women with endocrine-resistant disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results. Loibl, S., Turner, NC., Ro, J., et al.[2022]

In a phase II study involving 190 postmenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer, the combination of palbociclib and fulvestrant significantly improved one-year progression-free survival (PFS-1y) rates (83.5% vs. 71.9% for placebo) and median PFS (31.8 months vs. 22.0 months).

While the palbociclib/fulvestrant combination showed better efficacy, it was associated with higher rates of grade 3-4 adverse events, particularly neutropenia (68.1% vs. 0% in the placebo group), indicating a need for careful monitoring of side effects in patients receiving this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized phase II study of fulvestrant plus palbociclib or placebo in endocrine-sensitive, hormone receptor-positive/HER2-advanced breast cancer: GEICAM/2014-12 (FLIPPER). Albanell, J., Martínez, MT., Ramos, M., et al.[2022]

In a real-world study of 191 women with hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer, the combination of palbociclib and endocrine therapy showed a clinical benefit rate of 59.8%, with a median progression-free survival (PFS) of 13 months.

The treatment was more effective when given as a first-line therapy, resulting in a median PFS of 14 months, compared to shorter PFS durations in later treatment lines, indicating that earlier intervention may enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study. Palumbo, R., Torrisi, R., Sottotetti, F., et al.[2022]

In the CONFIRM study involving postmenopausal women with hormone receptor-positive advanced breast cancer, fulvestrant 500 mg significantly improved progression-free survival (PFS) compared to fulvestrant 250 mg, with a median PFS of 5.6 months versus 4.2 months in the first-line treatment setting.

Fulvestrant 500 mg also showed a trend towards improved overall survival (OS) in the second-line setting, with a median OS of 29.2 months compared to 22.8 months for the 250 mg dose, indicating its potential effectiveness in both treatment lines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-line vs second-line fulvestrant for hormone receptor-positive advanced breast cancer: A post-hoc analysis of the CONFIRM study. Di Leo, A., Jerusalem, G., Torres, R., et al.[2018]

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. 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 ...

3. 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.

4. 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 ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT400394

mBC who progressed on prior CDK4/6 inhibitors and ... Median progression-free survival was 24.7 wks (95% CI: 23.1, 47.4). At data cutoff, 8/26 (30.8%) pts with mBC continued PF-07220060 + ET without progression ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06105632

NCT06105632 | A Study to Learn About the ... The purpose of this study is to learn about the safety and how effective the study medicine (PF-07220060) plus fulvestrant is compared to the study doctor's ...

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. 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 ...