PF-07248144 + Fulvestrant for Breast Cancer

Recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must be taking: Endocrine therapy

Must not be taking: Chemotherapy

Disqualifiers: PIK3CA/AKT1/PTEN alterations, 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: 1

Duration: Multiple cycles of 28 days each

400 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment option for individuals with advanced or metastatic breast cancer that is hormone receptor-positive (HR-positive) and HER2-negative. Researchers aim to determine if a combination of two medicines, PF-07248144 (an experimental treatment) and fulvestrant, is safe and effective compared to current treatments. Participants will receive either this new combination or continue with a standard treatment of everolimus and hormone therapy. Ideal participants have breast cancer that worsened after previous CDK 4/6 inhibitor therapy. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study doctor, who can provide guidance based on your specific situation.

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

Previous studies have shown that the combination of PF-07248144 and fulvestrant is safe for people with HR-positive, HER2-negative metastatic breast cancer. Research indicates that patients tolerated the treatment well, and positive responses occurred in those who had already received treatment for this cancer type. The optimal dose of PF-07248144 was determined to be 5 mg per day, with an acceptable safety profile. While some side effects may occur, they are manageable and not too severe. However, the safety and effectiveness of PF-07248144 remain under investigation, as it is not yet approved for general use. ^{1 2 3 4 5}

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

Researchers are excited about PF-07248144 combined with fulvestrant for breast cancer because it targets cancer cells in a novel way. Unlike most treatments that focus on hormone receptors, PF-07248144 works by inhibiting specific proteins involved in cancer cell growth and survival, potentially offering a new approach for patients whose cancer has become resistant to standard hormone therapies. Additionally, the combination of a tablet (PF-07248144) and an injectable (fulvestrant) might provide a comprehensive treatment strategy, attacking the cancer on multiple fronts. This could be especially beneficial for those who have not responded well to traditional endocrine therapies like tamoxifen or aromatase inhibitors.

What evidence suggests that PF-07248144 plus fulvestrant might be an effective treatment for advanced or metastatic breast cancer?

Research has shown that the combination of PF-07248144 and fulvestrant, which participants in this trial may receive, has positive effects in treating patients with estrogen receptor-positive, HER2-negative metastatic breast cancer. Studies have found that this combination is safe and has led to positive responses in patients who have already tried other treatments. PF-07248144 blocks certain proteins, KAT6A and KAT6B, which help tumors grow. Early results suggest that targeting these proteins can slow cancer progression. Fulvestrant, a drug already used in breast cancer treatment, blocks estrogen receptors, reducing cancer cell growth. Overall, this new combination shows promise for patients with this type of advanced breast cancer. ^{1 2 3 4 6}

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 individuals with HR-positive, HER2-negative advanced or metastatic breast cancer that worsened after CDK 4/6 inhibitor therapy. Participants will receive either usual treatment (everolimus with exemestane or fulvestrant) or the study medicine PF-07248144 combined with fulvestrant.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My breast cancer is HR-positive, HER2-negative and cannot be removed by surgery or cured with radiation.

I've had CDK4/6 inhibitor therapy for advanced cancer and it progressed within 12 months after the last dose.

Exclusion Criteria

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

I have kidney, liver, or blood problems.

My cancer has specific genetic changes in PIK3CA, AKT1, or PTEN.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PF-07248144 in combination with fulvestrant or everolimus with endocrine therapy in 28-day cycles

Multiple cycles of 28 days each

Visits on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 3 Day 1

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PF-07248144

Trial Overview The trial tests PF-07248144 in tablet form taken daily at home, alongside fulvestrant injections at the clinic, against standard treatments. It aims to determine if this new combination is safe and effective for treating certain advanced breast cancers.

How Is the Trial Designed?

Group I: Arm A: PF-07248144 plus fulvestrant Experimental Treatment 2 Interventions

PF-07248144 tablet taken by mouth plus fulvestrant taken as a shot into the muscle.

Group II: Arm B: everolimus plus ET Active Control 3 Interventions

Everolimus tablet taken by mouth plus investigator's choice of endocrine therapy of exemestane tablet taken by mouth or fulvestrant taken as a shot into the muscle.

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07062965

NCT07062965 | A Study to Learn About the ... The study will compare the experiences of people receiving PF-07248144 in combination with fulvestrant to those of the people who do not. This will help see if ...

2. onclive.com onclive.com/view/pf-07248144-plus-fulvestrant-is-safe-active-in-pretreated-er-her2-metastatic-breast-cancer

PF-07248144 Plus Fulvestrant Is Safe, Active in Pretreated ... PF-07248144 plus fulvestrant was safe and generated responses in pretreated estrogen receptor–positive, HER2-negative metastatic breast cancer.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.1020

Dose optimization of PF-07248144, a first-in-class KAT6 ... 5 mg QD PF-07248144 was identified as the optimal dose in combination with FUL with acceptable safety and encouraging activity.

4. pfizeroncologydevelopment.com pfizeroncologydevelopment.com/clinical_trial/NCT07062965

Clinical Trial Details | Pfizer Oncology Development Website PF-07248144 is an investigational compound. Its safety and efficacy have not been established. An Interventional, Open-Label, Randomized, Multicenter, Phase 3 ...

5. nature.com nature.com/articles/s41591-024-03060-0

Inhibition of lysine acetyltransferase KAT6 in ER+HER2 Inhibition of histone lysine acetyltransferases (KATs) KAT6A and KAT6B has shown antitumor activity in estrogen receptor-positive (ER + ) breast cancer ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT04606446

Study of PF-07248144 in Advanced or Metastatic Solid ... A phase 1 dose expansion study of a first-in-class KAT6 inhibitor (PF-07248144) in patients with advanced or metastatic ER+ HER2− breast cancer.