Vepdegestrant + PF-07220060 for Breast Cancer

Recruiting at 61 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Pfizer

Must be taking: CDK4/6 inhibitors

Must not be taking: CYP3A inhibitors, QT prolongation drugs

Disqualifiers: Visceral crisis, Brain metastases, Cardiovascular diseases, others

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

Compensation: Varies

Number of Visits: 4

Duration: Up to approximately 1 year

65 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications, foods, or supplements that strongly affect specific liver enzymes (CYP3A or UGT2B7) or that can cause heart rhythm issues. It's best to discuss your current medications with the trial team to see if any need to be stopped.

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

Research shows that drugs like palbociclib, which is similar to PF-07220060, when combined with hormone therapy, can help women with certain types of breast cancer live longer without the disease getting worse. Additionally, drugs like elacestrant, which are similar to Vepdegestrant, have shown promise in reducing tumor growth in breast cancer models. ^{1 2 3 4 5}

What makes the drug Vepdegestrant + PF-07220060 unique for breast cancer treatment?

Vepdegestrant + PF-07220060 is unique because it combines a selective estrogen receptor degrader (SERD) with another agent, potentially offering a novel approach to targeting estrogen receptor-positive breast cancer by degrading the estrogen receptor and inhibiting its signaling, which may be more effective than existing treatments. ^{4 5 6 7 8}

What is the purpose of this trial?

The purpose of this study is to learn about the safety and effects of giving vepdegestrant along with PF-07220060. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat. The study is seeking for participants who have breast cancer that: * is hard to treat (advanced) and may have spread to other organs (metastatic). * is sensitive to hormonal therapy (it is called estrogen receptor positive). * is no longer responding to treatments taken before starting this study. All the participants will receive vepdegestrant and PF-07220060. Both medicines will be taken by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicines are safe and effective. Participants will continue to take vepdegestrant and PF-07220060 until: * their cancer is no longer responding, or * side effects become too severe. They will have visits at the study clinic about every 4 weeks.

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for people with advanced or metastatic breast cancer that's estrogen receptor positive and not responding to prior treatments. Participants should have at least one measurable lesion, be in good physical condition (ECOG PS ≤2), and must have had specific previous therapies including a CDK4/6 inhibitor regimen.

Inclusion Criteria

I have had one chemotherapy treatment for advanced/metastatic breast cancer, but no antibody-drug treatments.

I have a cancer lesion that can (or cannot) be measured by standard criteria.

I can care for myself and perform daily activities with little to no assistance.

Exclusion Criteria

I have kidney, liver, or bone marrow problems.

I have heart problems or significant heart disease.

I currently have an active infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vepdegestrant and PF-07220060 orally in 28-day cycles until cancer progression or severe side effects

Up to approximately 1 year

Visits at the study clinic about every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• PF-07220060
• Vepdegestrant

Trial Overview The study tests the combination of two oral medications, vepdegestrant and PF-07220060, as a potential treatment for tough-to-treat breast cancer that has spread. The effectiveness and safety of these drugs are being evaluated while participants take them at home until their cancer worsens or side effects become severe.

Participant Groups

Group I: vepdegestrant in combination with PF-07220060 Experimental Treatment 2 Interventions

vepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles

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

Arvinas Estrogen Receptor, Inc.

Industry Sponsor

Trials

19

Recruited

2,400+

Findings from Research

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]

Elacestrant, an oral selective estrogen receptor downregulator, was approved by the FDA in January 2023 for treating hormone receptor positive (HR+) HER2- advanced breast cancer, showing improved progression-free survival in patients with ESR1 mutations who had previously failed treatment with CDK 4/6 inhibitors and endocrine therapy.

Clinical trials indicate that elacestrant has a safety profile comparable to existing endocrine therapies and provides an effective alternative treatment option, especially for patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. Hageman, E., Lussier, ME.[2023]

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 presurgical study involving 46 women with ER+ HER2- breast cancer, AZD9496, an oral selective estrogen receptor degrader (SERD), demonstrated biological activity by reducing estrogen receptor (ER) levels, but was not superior to fulvestrant, the standard injectable SERD, in efficacy.

Both AZD9496 and fulvestrant effectively reduced progesterone receptor (PR) and Ki-67 levels, indicating their impact on tumor biology, but no new safety concerns were identified, suggesting that AZD9496 is safe to use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. Robertson, JFR., Evans, A., Henschen, S., et al.[2021]

Elacestrant (RAD1901) effectively degrades estrogen receptors and inhibits the growth of estrogen receptor-positive (ER+) breast cancer cells in both laboratory and patient-derived models, showing significant antitumor activity.

The combination of elacestrant with other therapies like palbociclib or everolimus enhances its efficacy, suggesting it could be a valuable treatment option for patients with ER+ breast cancer, including those with resistant mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. Bihani, T., Patel, HK., Arlt, H., et al.[2018]

Elacestrant (RAD-1901) is a selective estrogen receptor degrader that was approved by the USFDA for treating ER+ HER2-positive breast cancer, demonstrating anticancer activity in both laboratory and animal models.

The review discusses Elacestrant's development, including its medicinal chemistry, mechanism of action, and safety profile based on clinical trial data, highlighting its potential as an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. Bhatia, N., Thareja, S.[2023]

Fulvestrant, an estrogen receptor antagonist, was effective in treating advanced breast cancer in postmenopausal women, showing an overall clinical benefit in 39% of the 339 patients studied, with better outcomes when used as a first-line treatment.

The treatment was well tolerated, with only 5% of patients experiencing adverse events, and it was particularly beneficial for patients with tumors expressing both estrogen and progesterone receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. Steger, GG., Gips, M., Simon, SD., et al.[2018]

In a study of 26 postmenopausal women with hormone receptor-positive breast cancer, the combination of neoadjuvant chemotherapy and concurrent anastrozole resulted in a clinical complete response in 17.9% of patients and a clinical partial response in 57.1%.

The pathological complete response rate was 11.5%, indicating that the combined chemo-endocrine therapy was effective, but further research is needed to determine the specific contributions of the aromatase inhibitor versus the chemotherapy regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. Watanabe, N., Ootawa, Y., Kodama, K., et al.[2018]

References

1. 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]

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

Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. [2023]

3. 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]

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

A Randomized, Open-label, Presurgical, Window-of-Opportunity Study Comparing the Pharmacodynamic Effects of the Novel Oral SERD AZD9496 with Fulvestrant in Patients with Newly Diagnosed ER+ HER2- Primary Breast Cancer. [2021]

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

Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. [2018]

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

Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]

8. Japan pubmed.ncbi.nlm.nih.gov

Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. [2018]