Vepdegestrant + Samuraciclib for Advanced Breast Cancer

Recruiting at 46 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, CYP2D6 inhibitors

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: Until disease progression or unacceptable toxicity

11 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. 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. This study is divided into separate sub-studies. For Sub-Study C: All the participants will receive vepdegestrant and a medicine called samuraciclib. Vepdegestrant and samuraciclib will be taken once in a day 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 medicine is safe and effective. Participant will continue to take vepdegestrant and samuraciclib 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.

Do I need to stop my current medications for this trial?

The trial protocol does not specify if you must stop all current medications, but you cannot take medications, foods, or supplements that strongly affect certain liver enzymes (CYP3A, CYP2D6) or those that can cause heart rhythm issues.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot take certain medications, foods, or supplements that affect liver enzymes or heart rhythm. It's best to discuss your current medications with the trial team.

What data supports the idea that Vepdegestrant + Samuraciclib for Advanced Breast Cancer is an effective drug?

The available research does not provide specific data on the effectiveness of Vepdegestrant + Samuraciclib for Advanced Breast Cancer. Instead, it discusses other treatments like palbociclib combined with fulvestrant, which improved outcomes in certain breast cancer patients. Without direct data on Vepdegestrant + Samuraciclib, we cannot compare its effectiveness to these other treatments. ^{1 2 3 4 5}

What data supports the effectiveness of the drug combination Vepdegestrant + Samuraciclib for advanced breast cancer?

The research shows that similar drugs, like palbociclib combined with fulvestrant, have improved progression-free survival in advanced breast cancer. Additionally, selective estrogen receptor degraders (SERDs) like elacestrant have shown antitumor activity in breast cancer models, suggesting potential benefits of combining SERDs with other treatments. ^{1 2 3 4 5}

What safety data is available for Vepdegestrant and Samuraciclib in advanced breast cancer treatment?

The provided research does not contain specific safety data for Vepdegestrant (ARV-471, PF-07850327) and Samuraciclib in the treatment of advanced breast cancer. The studies listed focus on different chemotherapy regimens and treatments for breast and prostate cancer, but do not mention Vepdegestrant or Samuraciclib. Further research or clinical trial data specific to these drugs would be needed to answer the question. ^{6 7 8 9 10}

Is the drug Samuraciclib, Vepdegestrant a promising treatment for advanced breast cancer?

Yes, Samuraciclib, Vepdegestrant is a promising treatment for advanced breast cancer because it is being studied in combination with other drugs to improve outcomes for patients with this type of cancer. It aims to target specific pathways in cancer cells, potentially leading to better control of the disease. ^{1 2 5 11 12}

What makes the drug Vepdegestrant + Samuraciclib unique for advanced breast cancer?

Vepdegestrant + Samuraciclib is unique because it combines a selective estrogen receptor degrader (SERD) with a cyclin-dependent kinase inhibitor, potentially offering a novel approach to target estrogen receptor-positive breast cancer by degrading the receptor and inhibiting cell cycle progression, which may be effective even in cases resistant to other endocrine therapies. ^{1 2 5 11 12}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for individuals with advanced or metastatic breast cancer that's hormone-sensitive and not responding to prior treatments. Participants can have had up to two previous therapies for advanced disease, including one CDK4/6 inhibitor regimen, and must have at least one measurable lesion. They should be in a relatively stable condition (ECOG PS ≤1) without life-threatening visceral crises, significant lung function issues, recent other cancers except certain skin/cervix ones, inflammatory breast cancer, serious heart diseases or conditions affecting the kidneys, liver or bone marrow.

Inclusion Criteria

You have at least one specific type of visible abnormality that can be measured according to certain guidelines.

I am fully active and can carry on all pre-disease activities without restriction.

My breast cancer cannot be removed with surgery to cure it.

Exclusion Criteria

I have had lung problems caused by medication before.

I haven't had any cancer except for certain skin cancers or treated cervical cancer in the last 3 years.

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 samuraciclib orally once daily in 28-day cycles

Until disease progression or unacceptable toxicity

Visits at the study clinic about every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may continue treatment as long as they benefit and tolerate the medication

Long-term

Treatment Details

Interventions

• Samuraciclib
• Vepdegestrant

Trial Overview The study tests vepdegestrant combined with samuraciclib taken orally once daily at home by patients with tough-to-treat breast cancer. The goal is to determine the safety and effectiveness of this combination therapy in controlling cancer that has spread beyond the breast.

Participant Groups

Group I: ARV-471 in combination with Samuraciclib Experimental Treatment 2 Interventions

ARV-471 administered orally QD continuously and Samuraciclib administered orally QD 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+

Carrick Therapeutics Limited

Industry Sponsor

Trials

5

Recruited

290+

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]

The AMEERA-5 study is a phase 3 clinical trial involving 1066 patients with advanced ER+/HER2- breast cancer, comparing the efficacy and safety of amcenestrant plus palbociclib against letrozole plus palbociclib, with the primary goal of assessing progression-free survival.

Amcenestrant, an oral selective estrogen receptor degrader, has shown promising antitumor activity both alone and in combination with palbociclib, making it a potential first-line treatment option for patients who have not received prior systemic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer. Bardia, A., Cortes, J., Hurvitz, SA., et al.[2022]

The LORDSHIPS study found that a novel oral combination of dalpiciclib, pyrotinib, and letrozole showed a promising objective response rate of 66.7% in patients with HER2-positive, hormone receptor-positive metastatic breast cancer, indicating its efficacy as a treatment option.

The most common severe side effects included neutropenia and leukopenia, but the treatment demonstrated a median progression-free survival of 11.3 months, suggesting it is a viable chemotherapy-sparing option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. Zhang, J., Meng, Y., Wang, B., et al.[2022]

In a study of 247 patients with metastatic hormone receptor-positive, PIK3CA-mutant breast cancer, 61.5% developed any-grade hyperglycemia after treatment with alpelisib, with a median onset time of just 16 days.

Patients receiving alpelisib as standard care experienced significantly higher rates of hyperglycemia compared to those in clinical trials, highlighting the importance of monitoring and optimizing glycemic status before starting treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. Shen, S., Chen, Y., Carpio, A., et al.[2023]

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]

In a study of 125 breast cancer patients receiving high-dose chemotherapy, a comprehensive supportive care approach resulted in a low treatment-related mortality rate of less than 1%, indicating that this strategy can enhance safety during aggressive treatment.

Despite significant nonhematologic toxicities such as diarrhea (66%) and stomatitis (33%), infectious complications were rare, suggesting that with proper supportive care, high-dose chemotherapy can be administered with manageable risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care. Holland, HK., Dix, SP., Geller, RB., et al.[2017]

The combination of vinorelbine, fluorouracil, and leucovorin (ViFL) demonstrated a 27.5% overall response rate and a 76.5% disease control rate in 51 women with metastatic breast carcinoma previously treated with other chemotherapy agents, indicating its potential efficacy.

The treatment was generally well-tolerated, with manageable side effects; however, the low response rate suggests that ViFL may not be suitable for use before surgery (neoadjuvant setting).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine and fluorouracil plus leucovorin combination (ViFL) in patients with anthracycline and taxane-pretreated metastatic breast cancer: a phase II study. Oliva, C., Bergnolo, P., Inguì, M., et al.[2021]

In a study of 52 patients with androgen-resistant prostate cancer, the combination of docetaxel, vinorelbine, and oral estramustine resulted in a significant prostate-specific antigen (PSA) response of 56%, indicating effective treatment.

The regimen was generally well-tolerated, with mild toxicity observed; however, 33% of patients experienced severe neutropenia, highlighting the need for monitoring blood cell counts during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with docetaxel, vinorelbine and estramustine phosphate in metastatic androgen-resistant prostate cancer: a single institution experience. Pectasides, D., Pectasides, E., Papaxoinis, G., et al.[2018]

The combination of vinorelbine (VRL) and hydrocortisone significantly improved progression-free survival (PFS) and prostate-specific antigen (PSA) response rates in patients with hormone-refractory prostate cancer compared to hydrocortisone alone, with 6-month PFS rates of 33.2% versus 22.8%.

VRL plus hydrocortisone was well tolerated among elderly patients, showing a low incidence of severe side effects, making it a safe treatment option despite not improving overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Abratt, RP., Brune, D., Dimopoulos, MA., et al.[2020]

The combination of vinorelbine and estramustine was found to be a well-tolerated treatment for 25 men with androgen-independent metastatic prostate cancer, with mild gastrointestinal side effects and minimal hematologic toxicity.

This treatment led to a significant decrease in prostate-specific antigen (PSA) levels in 24% of patients, with a median duration of response of 10 weeks, although no complete or partial responses were observed in measurable disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vinorelbine and estramustine in androgen-independent metastatic prostate cancer: a phase II study. Smith, MR., Kaufman, D., Oh, W., et al.[2019]

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]

Fulvestrant is the only approved selective estrogen receptor degrader (SERD) for treating estrogen receptor-positive advanced breast cancer, primarily used in the second-line setting after progression on aromatase inhibitors.

Combining fulvestrant with CDK4/6 inhibitors has demonstrated significant benefits compared to using fulvestrant alone, indicating a potential strategy to improve outcomes for patients with endocrine-resistant breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of fulvestrant for the treatment of metastatic breast cancer. Soleja, M., Raj, GV., Unni, N.[2019]

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

AMEERA-5: a randomized, double-blind phase 3 study of amcenestrant plus palbociclib versus letrozole plus palbociclib for previously untreated ER+/HER2- advanced breast cancer. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Dalpiciclib Combined With Pyrotinib and Letrozole in Women With HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer (LORDSHIPS): A Phase Ib Study. [2022]

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

Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]

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

Minimal toxicity and mortality in high-risk breast cancer patients receiving high-dose cyclophosphamide, thiotepa, and carboplatin plus autologous marrow/stem-cell transplantation and comprehensive supportive care. [2017]

7. Germany pubmed.ncbi.nlm.nih.gov

Vinorelbine and fluorouracil plus leucovorin combination (ViFL) in patients with anthracycline and taxane-pretreated metastatic breast cancer: a phase II study. [2021]

8. Greece pubmed.ncbi.nlm.nih.gov

Combination chemotherapy with docetaxel, vinorelbine and estramustine phosphate in metastatic androgen-resistant prostate cancer: a single institution experience. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. [2020]

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

Vinorelbine and estramustine in androgen-independent metastatic prostate cancer: a phase II study. [2019]

11. Netherlands pubmed.ncbi.nlm.nih.gov

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

12. England pubmed.ncbi.nlm.nih.gov

An evaluation of fulvestrant for the treatment of metastatic breast cancer. [2019]