Vepdegestrant + Samuraciclib for Advanced Breast Cancer

Not currently recruiting at 51 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining vepdegestrant and samuraciclib can safely and effectively treat advanced breast cancer that has spread. Researchers are studying vepdegestrant for its potential to aid in cases where cancer is difficult to treat, especially when it responds to hormonal therapy but has stopped responding to previous treatments. Participants will take both medications daily at home. The trial seeks individuals with breast cancer that is hard to treat, has potentially spread, and has stopped responding to past treatments. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering participants the chance to contribute to groundbreaking cancer research.

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.

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

Research has shown that vepdegestrant, when used alone, is well tolerated by patients with advanced breast cancer. One study found that it helped some patients without causing serious side effects.

When combined with another medicine, vepdegestrant produced positive results for many patients without major safety concerns.

Less information is available about samuraciclib on its own, but the combination with vepdegestrant is under careful study to ensure safety. As this trial is in the early stages, it aims to gather more information on how well patients tolerate the combination. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Vepdegestrant and Samuraciclib for advanced breast cancer because it offers a novel approach to treatment. Vepdegestrant is a selective estrogen receptor degrader (SERD), targeting and breaking down estrogen receptors, which are often implicated in breast cancer growth. Samuraciclib is a CDK7 inhibitor that disrupts the cancer cell cycle, preventing the cells from multiplying. This combination could potentially be more effective than current treatments by simultaneously attacking cancer from different angles, offering hope for better outcomes in patients with advanced stages of the disease.

What evidence suggests that vepdegestrant and samuraciclib could be effective for advanced breast cancer?

This trial will evaluate the combination of vepdegestrant and samuraciclib for treating advanced breast cancer. Studies have shown that this combination could be promising. Vepdegestrant targets and breaks down the estrogen receptor in cancer cells, which is crucial because many advanced breast cancers grow due to estrogen. In earlier research, vepdegestrant, when combined with another drug, improved or stabilized cancer in 62.5% of patients, and 26.7% of patients experienced tumor shrinkage. Samuraciclib blocks enzymes that aid cancer cell growth, further inhibiting the cancer. Together, these drugs aim to fight cancer more effectively by blocking its growth and survival. ^{2 3 5 6 7}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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 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]

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]

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]

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 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]

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 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]

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]

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]

Citations

1. carricktherapeutics.com carricktherapeutics.com/investors/news-events/press-releases/detail/19/carrick-therapeutics-announces-clinical-trial-collaboration

Press Releases Vepdegestrant is an investigational, orally-bioavailable PROTAC® protein degrader designed to specifically target and degrade the estrogen ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11524203/

VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER ... The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast ...

3. pfizer.com pfizer.com/news/press-release/press-release-detail/arvinas-and-pfizer-announce-initial-phase-1b-data-tactive-u

Arvinas and Pfizer Announce Initial Phase 1b Data from the ... Vepdegestrant in combination with abemaciclib demonstrated encouraging clinical activity (clinical benefit rate: 62.5%; overall response rate: 26.7%)

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05463952

A Study to Learn About the Vepdegestrant (ARV-471, PF- ... The purpose of this clinical trial is to learn about the safety, tolerability, Pharmacokinetics (PK), and preliminary efficacy of ARV-471 as monotherapy in ...

5. ir.arvinas.com ir.arvinas.com/news-releases/news-release-details/arvinas-and-pfizers-vepdegestrant-arv-471-receives-fda-fast

Arvinas and Pfizer's Vepdegestrant (ARV-471) Receives ... Vepdegestrant is an investigational PROteolysis Targeting Chimera (PROTAC ® ) protein degrader designed to target and degrade the estrogen receptor (ER) ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06125522

NCT06125522 | TACTIVE-U: A Study to Learn About the ... 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 ...

7. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-vepdegestrant-and-samuraciclib-for-adults-with-er-advanced-or-metastatic-breast-cancer/

Study on the Safety and Effectiveness of Vepdegestrant ... This study examines the safety and effectiveness of Vepdegestrant and Samuraciclib in treating adults with ER+ advanced or metastatic breast cancer.