Vepdegestrant + PF-07220060 for Breast Cancer
Palo Alto (17 mi)Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: Pfizer
No Placebo Group
Trial Summary
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.
What data supports the idea that Vepdegestrant + PF-07220060 for Breast Cancer is an effective drug?The available research does not provide specific data on the effectiveness of Vepdegestrant + PF-07220060 for breast cancer. Instead, it discusses other treatments like palbociclib and elacestrant, which have shown effectiveness in treating hormone receptor-positive, HER2-negative breast cancer. For example, palbociclib combined with endocrine therapy has been shown to prolong the time patients live without the cancer getting worse. Elacestrant has also shown promise in reducing tumor growth in certain breast cancer models. However, there is no direct comparison or data available for Vepdegestrant + PF-07220060 in the provided information.345610
Is the drug PF-07220060, also known as Vepdegestrant, a promising treatment for breast cancer?Yes, Vepdegestrant, also known as PF-07220060, is a promising drug for breast cancer. It is part of a new class of drugs called selective estrogen receptor degraders (SERDs), which are designed to target and break down estrogen receptors in cancer cells. This can help stop the growth of certain types of breast cancer that rely on estrogen. The drug has shown potential in preclinical studies and is being tested in combination with other treatments to improve its effectiveness.12458
What safety data is available for the treatment Vepdegestrant + PF-07220060 in breast cancer?The provided research does not directly address the safety data for Vepdegestrant + PF-07220060. However, it discusses Elacestrant (RAD1901), a selective estrogen receptor degrader (SERD), which has been approved by the FDA for breast cancer treatment. Elacestrant has shown anticancer activity in ER+ HER2-positive breast cancer models and has been evaluated in clinical trials, including the phase 3 EMERALD trial, which demonstrated improved progression-free survival. The safety profile of Elacestrant has been discussed in these studies, but specific safety data for the combination of Vepdegestrant + PF-07220060 is not provided in the available research.45789
Do I have to stop taking my current medications for the trial?The trial protocol does not specify if you must stop taking your current medications. However, you cannot take medications, foods, or supplements that strongly affect certain liver enzymes (CYP3A or UGT2B7) or drugs that can cause heart rhythm issues.
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 can care for myself and perform daily activities with little to no assistance.
I have been treated with a CDK4/6 inhibitor before.
My breast cancer cannot be removed with surgery to cure it.
Exclusion Criteria
I have heart problems or significant heart disease.
I currently have an active infection.
My condition is critical, with life-threatening complications.
Treatment Details
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.
1Treatment groups
Experimental Treatment
Group I: vepdegestrant in combination with PF-07220060Experimental Treatment2 Interventions
vepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles
Find a clinic near you
Research locations nearbySelect from list below to view details:
START MidwestGrand Rapids, MI
Clinical and Translational Research Unit (CTRU)Palo Alto, CA
Stanford Cancer CenterPalo Alto, CA
Stanford Cancer Institute - Clinical Trials OfficePalo Alto, CA
More Trial Locations
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Who is running the clinical trial?
PfizerLead Sponsor
Arvinas Estrogen Receptor, Inc.Industry Sponsor
References
Fulvestrant ("Faslodex"): clinical experience from the Compassionate Use Programme. [2018]Fulvestrant ("Faslodex") is a new oestrogen receptor (ER) antagonist with no agonist effects that is licensed in the USA, Brazil, Europe and elsewhere for the treatment of advanced breast cancer (ABC) in postmenopausal women following progression on other endocrine agents. This report consolidates clinical experience from the "Faslodex" Compassionate Use Programme, including a total of 339 patients treated at eight cancer centres. Patients received fulvestrant as first- (n=22), second- (n=125), third- (n=105), fourth- (n=58), fifth- (n=22) or sixth-line (n=5) hormonal treatment for ABC, with two patients receiving fulvestrant after more than six other endocrine therapies. Objective response was achieved by 40 patients and stable disease lasting 6 months by 92 patients, giving overall clinical benefit (CB) in 132/339 patients (39%). The CB rate decreased as fulvestrant was used later in the sequence of endocrine treatments, from 46% (10/22) with first-line fulvestrant to 27% (6/22) with fifth-line fulvestrant. Increased benefit was found in patients with tumours expressing both ER and progesterone receptor (PgR) compared with other combinations, although good activity was reported in patients expressing either ER or PgR as well as in tumours expressing human epidermal growth factor receptor 2. Fulvestrant was well tolerated; adverse events were noted in 18/339 patients (5%). These findings concur with data from the clinical-trial setting and further support the assertion that greater benefit is derived when fulvestrant is used early in the treatment sequence.
Concurrent administration of chemo-endocrine therapy for postmenopausal breast cancer patients. [2018]We have been treating hormone receptor-positive, postmenopausal women with breast cancer with a regimen of neoadjuvant chemotherapy (NAC), FEC (fluorouracil, epirubicin, and cyclophosphamide), followed by weekly doses of paclitaxel combined with the concurrent administration of anastrozole. In this article, we compared our results retrospectively with those of past trials.
Palbociclib: a first-in-class CDK4/CDK6 inhibitor for the treatment of hormone-receptor positive advanced breast cancer. [2022]Palbociclib was approved by the FDA for use in combination with letrozole for the treatment of postmenopausal women with hormone-receptor-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy. In addition, the combination of palbociclib with fulvestrant resulted in superior outcome than fulvestrant alone in those who had progressed during prior endocrine therapy. This research highlight summarized the current development of CDK4/CDK6 inhibitors and future directions in the treatment of advanced hormone-receptor-positive breast cancer.
Elacestrant (RAD1901), a Selective Estrogen Receptor Degrader (SERD), Has Antitumor Activity in Multiple ER+ Breast Cancer Patient-derived Xenograft Models. [2018]Purpose: Estrogen receptor-positive (ER+) breast cancers are typically treated with endocrine agents, and dependence on the ER pathway is often retained even after multiple rounds of antiestrogen therapy. Selective estrogen receptor degraders (SERD) are being developed as a strategy to more effectively target ER and exploit ER dependence in these cancers, which includes inhibiting both wild-type and mutant forms of ER. The purpose of this study was to evaluate the efficacy of a novel orally bioavailable SERD, elacestrant (RAD1901), in preclinical models of ER+ breast cancer.Experimental Design: Elacestrant was evaluated as a single agent and in combination with palbociclib or everolimus in multiple ER+ breast cancer models, including several patient-derived xenograft models.Results: Elacestrant induces the degradation of ER, inhibits ER-mediated signaling and growth of ER+ breast cancer cell lines in vitro and in vivo, and significantly inhibits tumor growth of multiple PDX models. Furthermore, we demonstrate that elacestrant in combination with palbociclib or everolimus can lead to greater efficacy in certain contexts. Finally, elacestrant exhibits significant antitumor activity both as a single agent and in combination with palbociclib in two patient-derived breast cancer xenograft models harboring ESR1 mutations.Conclusions: These data underscore the potential clinical utility of elacestrant as a single agent and as a combination therapy, for both early- and late-stage ER+ disease. Clin Cancer Res; 23(16); 4793-804. ©2017 AACR.
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]Label="PURPOSE">Fulvestrant, the first-in-class selective estrogen receptor (ER) degrader (SERD), is clinically effective in patients with ER+ breast cancer, but it has administration and pharmacokinetic limitations. Pharmacodynamic data suggest complete ER degradation is not achieved at fulvestrant's clinically feasible dose. This presurgical study (NCT03236974) compared the pharmacodynamic effects of fulvestrant with AZD9496, a novel, orally bioavailable, nonsteroidal, potent SERD, in treatment-naïve patients with ER+ HER2- primary breast cancer awaiting curative intent surgery.
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]The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials.
Targeting the Progesterone Receptor in Breast Cancer: Mind the Short Form! [2023]The presurgical window of opportunity trial (WOT) MIPRA provides evidence that neoadjuvant treatment with the progesterone receptor (PR) antagonist mifepristone (RU486) may benefit patients with estrogen receptor-positive (ER+) breast cancer characterized by a high ratio of PR-A versus PR-B isoform (>1.5), suggesting that PR may be targeted in a subset of patients. See related article by Elía et al., p. 866.
Elacestrant: a new FDA-approved SERD for the treatment of breast cancer. [2023]Elacestrant (RAD-1901), a selective estrogen receptor degrader, was approved by USFDA on January 27, 2023, for the treatment of breast cancer. It has been developed by Menarini Group under the brand name Orserdu®. Elacestrant showed anticancer activity both in vitro and in vivo in ER+ HER2-positive breast cancer models. The present review delebrates the development stages of Elacestrant, with its medicinal chemistry, synthesis, mechanism of action, and pharmacokinetic studies. Clinical data and safety profile has also been discussed, including data from randomized trials.
Pharmacology and pharmacokinetics of elacestrant. [2023]Elacestrant, a novel oral selective estrogen receptor (ER) degrader (SERD), was approved by the Food and Drug Administration (FDA) on January 27, 2023, for use in patients with ER and/or progesterone receptor (PR)-positive and HER2-negative metastatic breast cancer whose tumors harbor an ESR1 missense mutation (ESR1-mut), after at least one line of endocrine therapy (ET). The FDA made its decision based on the randomized phase 3 EMERALD trial, which met its primary endpoint of improved median progression-free survival (mPFS) with elacestrant monotherapy versus standard-of-care endocrine monotherapy in the overall intention to treat population; however, this benefit was largely driven by the ESR1-mut cohort. Elacestrant is a dose-dependent mixed ER agonist/antagonist, which at high doses acts as a direct ER antagonist as well as selective downregulator of ER. It is 11% bioavailable, primarily metabolized by CYP3A4 in the liver and excreted in feces. This leads to drug-drug interactions with strong CYP3A4 inhibitors and inducers, such as itraconazole and rifampin, respectively. In accordance with its clearance route, dose reduction is recommended in patients with moderate hepatic dysfunction but not in renal dysfunction. Studies evaluating elacestrant in severe hepatic dysfunction as well as in patients from racial and ethnic minority groups are ongoing. Overall, elacestrant is the first orally bioavailable SERD approved by the FDA for use in patients with metastatic breast cancer. Current clinical trials are ongoing evaluating it in the adjuvant setting in patients with early stage ER-positive breast cancers.
Elacestrant for ER-Positive HER2-Negative Advanced Breast Cancer. [2023]This article aims to discuss elacestrant, an oral selective estrogen receptor downregulator approved by the Food and Drug Administration (FDA) in January 2023 for the treatment of hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer.