PF-07220060 + Fulvestrant for Advanced Breast Cancer

Recruiting at 244 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

333 Participants Needed

Trial Summary

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.

What data supports the idea that PF-07220060 + Fulvestrant for Advanced Breast Cancer is an effective treatment?

The available research shows that a similar drug, palbociclib, when combined with fulvestrant, significantly improved the time patients lived without their cancer getting worse compared to fulvestrant alone. This was observed in multiple studies, including the FLIPPER and PALOMA-3 trials. These studies suggest that combining a drug like PF-07220060 with fulvestrant could also be effective for treating advanced breast cancer. ^{1 2 3 4 5}

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

Research on similar drugs like palbociclib, when combined with fulvestrant, has shown improved progression-free survival (the time during which the cancer does not get worse) in patients with hormone receptor-positive, HER2-negative advanced breast cancer. ^{1 2 3 4 5}

What safety data exists for PF-07220060 + Fulvestrant in advanced breast cancer treatment?

The provided research does not contain specific safety data for PF-07220060 (Atirmociclib) combined with Fulvestrant. Instead, it discusses the safety and efficacy of Palbociclib, another CDK4/6 inhibitor, combined with Fulvestrant. In these studies, neutropenia was the most common adverse event associated with Palbociclib. However, this information may not directly apply to PF-07220060, and specific safety data for PF-07220060 would need to be obtained from studies directly evaluating this treatment combination. ^{1 3 5 6 7}

Is the drug PF-07220060 (Atirmociclib) combined with Fulvestrant promising for advanced breast cancer?

Yes, combining PF-07220060 with Fulvestrant is promising for advanced breast cancer because Fulvestrant is effective in treating hormone-sensitive breast cancer, especially in postmenopausal women. It works by blocking and breaking down estrogen receptors, which helps slow down cancer growth. Fulvestrant has shown good results when used alone or with other treatments, making it a valuable option in advanced breast cancer care. ^{8 9 10 11 12}

How is the drug PF-07220060 + Fulvestrant unique for advanced breast cancer?

The combination of PF-07220060 (Atirmociclib) and Fulvestrant is unique because it pairs a novel CDK inhibitor with a selective estrogen receptor degrader (SERD), potentially offering a new approach to target hormone receptor-positive advanced breast cancer by both blocking cell cycle progression and degrading estrogen receptors. ^{8 9 10 11 12}

What is the purpose of this trial?

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 choice of treatment in people with advanced or metastatic breast cancer. Advanced cancer is the one that is unlikely to be cured or taken care of with treatment. Metastatic cancer is the one that has spread to other parts of the body. This study is seeking female and male participants who: * are 18 years of age or older; * are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative; * have advanced or metastatic breast cancer after taking other treatments before this study; * have not taken or need to take medications that are not allowed by the study protocol; * do not have any medical or mental conditions that may increase the risk of study participation. Half of the participants will take PF-07220060 two times daily by mouth along with fulvestrant. Fulvestrant will be given as a shot into the muscle. The other half will take the study doctor's choice of treatment which can either be: * Fulvestrant alone taken as shot into the muscle. * Everolimus along with exemestane taken once daily by mouth. This study will compare the experiences of participants receiving the study medicine plus fulvestrant to those who are receiving the study doctor's choice of treatment. This will help decide if the study medicine is safe and effective. Participants will receive study treatment and/or will be in the study until: * imaging scans (such as an MRI and/or CT) show that their cancer is getting worse. * the study doctor thinks the participant is no longer benefitting from the study medicine. * has side effects that become too severe. A side effect is a reaction (expected or unexpected) to a medicine or treatment you take. * the participant chooses to stop taking part.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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 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 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]

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 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]

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]

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 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]

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]

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]

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]

References

1. England 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. [2023]

2. England 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). [2022]

3. England 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. [2022]

4. England 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. [2022]

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

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

6. Korea (South) 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. [2021]

7. England 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. [2022]

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

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

9. Netherlands 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. [2018]

10. England pubmed.ncbi.nlm.nih.gov

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

11. Italy pubmed.ncbi.nlm.nih.gov

Efficacy of fulvestrant in the treatment of postmenopausal women with endocrine-resistant advanced breast cancer in routine clinical practice. [2022]

12. New Zealand 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. [2020]