A PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD, SINGLE-DOSE, CROSS-OVER STUDY TO ESTIMATE THE ABSOLUTE BIOAVAILABILITY OF VEPDEGESTRANT (ARV-471, PF-07850327) FOLLOWING ORAL AND INTRAVENOUS DOSING OF THE DRUG TO HEALTHY PARTICIPANTS

The purpose of this study is to learn how much of the study medicine called Vepdegestrant will reach the bloodstream when given orally compared to given intravenously.
This study is seeking participants who:
* are healthy males and healthy females who cannot have children.
* are 18 years or older.
* are healthy as decided by medical tests.
* have a body mass index (BMI) of 16 to 32 kilogram per meter squared.
* have a total body weight of more than 45 kilograms (99 pounds).
In Period 1, all participants will receive one dose of Vepdegestrant by IV. In Period 2, all participants will receive one dose of Vepdegestrant by mouth following a high-fat breakfast. The levels of Vepdegestrant in Period 1 will be compared to the levels of Vepdegestrant in Period 2 and the bioavailablility of the oral formulation of Vepdegestrant will be determined.
The study duration is 22 days and includes two periods. Participants will stay in the clinical research unit for 9 days (8 nights) during each period. A follow-up visit for each participant takes place at 28 to 35 days after taking the study medicine for the last time.

Start Date03 Apr 2025

Sponsor / Collaborator

Pfizer Inc.

[+1]

CTR20242782

/ Active, not recruitingPhase 2

一项在 18 岁及以上 ER+/HER2- 晚期或转移性乳腺癌研究参与者中评估口服蛋白水解靶向嵌合体 Vepdegestrant（ARV-471/PF-07850327）联合 PF-07220060 治疗的耐受性、PK 和抗肿瘤活性的开放标签、干预性的安全有效性 Ib/II 期研究

[Translation] An open-label, interventional, phase Ib/II safety-effectiveness study evaluating the tolerability, PK, and antitumor activity of the oral proteolysis-targeted chimeric vepdegestrant (ARV-471/PF-07850327) in combination with PF-07220060 in participants aged 18 years and older with ER+/HER2- advanced or metastatic breast cancer

II期主要目的：1. 评估 Vepdegestrant 联合 PF-07220060 治疗的临床抗肿瘤活性。II期次要目的：1. 确定 Vepdegestrant 联合 PF-07220060 治疗的其他抗肿瘤活性结局。2. 进一步评价 Vepdegestrant 与 PF-07220060 联合用药的总体安全性特征和耐受性。3. 评价 Vepdegestrant 与 PF-07220060 联合给药时，Vepdegestrant、ARV-473 和 PF-07220060 的血浆药物暴露量。4. 评估治疗后血浆 ctDNA 相对于基线水平的变化。II期探索性目的：1. 探索 PF-07220060 联合 Vepdegestrant 治疗对患者报告的症状和健康相关生命质量的影响。2. 了解乳腺癌的肿瘤生物学，确定潜在的敏感性和/或耐药性机制。3. 评价分子定义的研究参与者人群中突变状态与应答之间的关系。4. 探索药物基因组学对 PF-07220060 血浆药物暴露量的影响。

[Translation]

Phase II primary objectives: 1. To evaluate the clinical anti-tumor activity of Vepdegestrant combined with PF-07220060. Phase II secondary objectives: 1. To determine other anti-tumor activity outcomes of Vepdegestrant combined with PF-07220060. 2. To further evaluate the overall safety profile and tolerability of Vepdegestrant combined with PF-07220060. 3. To evaluate the plasma drug exposure of Vepdegestrant, ARV-473, and PF-07220060 when Vepdegestrant is administered in combination with PF-07220060. 4. To evaluate the change in plasma ctDNA levels relative to baseline after treatment. Phase II exploratory objectives: 1. To explore the effect of PF-07220060 combined with Vepdegestrant on patient-reported symptoms and health-related quality of life. 2. Understand the tumor biology of breast cancer and identify potential mechanisms of sensitivity and/or resistance. 3. Evaluate the relationship between mutation status and response in a molecularly defined population of study participants. 4. Explore the impact of pharmacogenomics on plasma drug exposure to PF-07220060.

Start Date18 Nov 2024

Sponsor / Collaborator

Pfizer Inc.

[+2]

NCT06645938

/ CompletedPhase 1

A PHASE I, RANDOMIZED, OPEN-LABEL, 2-PERIOD, 2-TREATMENT, 2-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY IN HEALTHY ADULT PARTICIPANTS TO ESTIMATE THE BIOAVAILABILITY OF AN VARIANT (HIGH HARDNESS) TABLET OF VEPDEGESTRANT (ARV-471, PF-07850327) RELATIVE TO THE REGISTRATIONAL TABLET

The purpose of the study is to compare the amount vepdegestrant available from two different tablet formulations under fed conditions in healthy adult participants; 200 mg vepdegestrant alternative tablet formulation compared to 200 mg vepdegestrant standard tablet formulation.
This study is seeking male or female participants of non-childbearing potential age who:
* are 18 years or older
* are healthy as decided by medical tests.
* have a Body mass index (BMI) of 16 to 32 kilogram per meter squared; and a total body weight of more than 45 kilograms (99 pounds).
All participants will be put into groups to receive one of the 2 treatments in each period. This study will consist of 2 treatment sequences:
* Sequence 1: Single 200 mg dose of vepdegestrant registrational tablet in Period 1, followed by a single 200 mg dose of vepdegestrant variant tablet in Period 2.
* Sequence 2: Single 200 mg dose of vepdegestrant variant tablet in Period 1, followed by a single 200 mg dose of vepdegestrant registrational tablet in Period 2.
Participants will be in the study for about 11 weeks.

Start Date16 Oct 2024

Sponsor / Collaborator

Pfizer Inc.

[+1]

100 Clinical Results associated with Vepdegestrant

100 Translational Medicine associated with Vepdegestrant

100 Patents (Medical) associated with Vepdegestrant

Literatures (Medical) associated with Vepdegestrant

01 Aug 2025·MOLECULAR DIVERSITY

AI-DPAPT: a machine learning framework for predicting PROTAC activity

Article

Author: Alshammari, Bahaa ; Alqarni, Saad ; Kassab, Shaymaa E. ; Abouzied, Amr S. ; Abouzied, Amr S ; Kari, Hayam ; Huwaimel, Bader ; Kassab, Shaymaa E

Proteolysis Targeting Chimeras are part of targeted protein degradation (TPD) techniques, which are significant for pharmacological and therapy development. Small-molecule interaction with the targeted protein is a complicated endeavor and a challenge to predict the proteins accurately. This study used machine learning algorithms and molecular fingerprinting techniques to build an AI-powered PROTAC Activity Prediction Tool that could predict PROTAC activity by examining chemical structures. The chemical structures of a diverse set of PROTAC drugs and their corresponding activities are selected as a dataset for training the tool. The processes used in this study included data preparation, feature extraction, and model training. Further, evaluation was done for the performance of the various classifiers, such as AdaBoost, Support Vector Machine, Random Forest, Gradient Boosting, and Multi-Layer Perceptron. The findings show that the methods selected here depict accurate PROTAC activities. All the models in this study showed an ROC curve better than 0.9, while the random forest on the test set of the AI-DPAPT had an area under the curve score of 0.97, thus showing accurate results. Furthermore, the study revealed significant insights into the molecular features that can influence the functions of the PROTAC. These findings can potentially increase the understanding of the structure-activity correlations involved in the TPD. Overall, the investigation contributes to computational drug development by introducing this platform powered by artificial intelligence that predicts the function of PROTAC. In addition, it sped up the processes of identifying and improving previously unknown medications. The AI-DPAPT platform can be accessed online using a web server at https://ai-protac.streamlit.app/ .

01 Jun 2025·EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS

A comprehensive mechanistic investigation of factors affecting intestinal absorption and bioavailability of two PROTACs in rats

Article

Author: Dahlgren, David ; Koziolek, Mirko ; Borchardt, Thomas ; Arendt, Nathalie ; Sjöblom, Markus ; Indulkar, Anura ; Hedeland, Mikael ; Dubbelboer, Ilse R ; Niessen, Janis ; Lennernäs, Hans

AIM:

Proteolysis targeting chimeras (PROTACs) exhibit a unique and promising pharmacology. However, this comes with molecular properties exceeding the 'drug-like' rule of five chemical space, which often limits gastrointestinal absorption. This in vivo study aimed to investigate the contribution of luminal and plasma stability, intestinal effective permeability, P-glycoprotein (P-gp) efflux, and bile excretion, on the rat intestinal absorption and systemic exposure of two PROTACs, ARV-110 (812 Da, LogD_7.4 4.8) and ARV-471 (724 Da, LogD_7.4 4.6).

METHODS:

Luminal stability and effective intestinal permeability were determined directly from luminal disappearance using single-pass intestinal perfusion, with and without a protease inhibitor, or a P-gp/Cytochrome P450 CYP3A inhibitor (ketoconazole) in rats. Plasma stability was tested by in vitro incubations. Intestinal absorption, systemic exposure, and biliary excretion were examined after intraduodenal and intravenous dosing with ketoconazole or the P-gp selective inhibitor (encequidar).

RESULTS AND DISCUSSION:

Both PROTACs were degraded in the intestinal lumen and in plasma by peptidases. The intestinal effective permeability in rats was moderate for ARV-110 (0.62 × 10^-4 cm/s) and low for ARV-471 (0.23 × 10^-4 cm/s). P-gp inhibition increased the permeability 1.6- and 2.3-fold for ARV-110 and ARV-471, respectively. After intraduodenal dosing with the P-gp inhibitors a corresponding increase in systemic exposure was observed for both PROTACs. There was only a minor difference in the increased systemic exposure induced by the two inhibitors, suggesting that the mechanisms were primarily P-gp inhibition, rather than gut-wall and hepatic extraction. Biliary excretion was a minor pathway and did not affect the absorption and systemic exposure of the PROTACs to a large extent.

CONCLUSION:

In the rat, ARV-110 and ARV-471 were enzymatically degraded in the intestinal lumen and in plasma, and their intestinal permeability and systemic exposure seem to be reduced due to P-gp efflux.

31 May 2025·NEW ENGLAND JOURNAL OF MEDICINE

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer.

Article

Author: Hu, Xichun ; Parameswaran, Janaki ; Mouret-Reynier, Marie-Ange ; Lu, Dongrui R ; Jerzak, Katarzyna J ; Hamilton, Erika P ; Patsouris, Anne ; Zhi, Xin ; Valota, Olga ; Guarneri, Valentina ; Cui, Jiuwei ; De Laurentiis, Michelino ; Sezer, Ahmet ; Jhaveri, Komal ; Yoshinami, Tetsuhiro ; Fontana, Andrea ; Zamagni, Claudio ; Cil, Timucin ; Martignoni, Marcella ; Molckovsky, Andrea ; Ladoire, Sylvain ; Rodriguez-Lescure, Alvaro ; Zhang, Yongqiang ; Fuentes, Christian ; Demirci, Umut ; Campone, Mario ; Cazzaniga, Marina

BACKGROUND:

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin-proteasome system.

METHODS:

In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had received one previous line of cyclin-dependent kinase 4 and 6 inhibitor therapy plus one line of endocrine therapy (and up to one additional line of endocrine therapy). Patients were randomly assigned in a 1:1 ratio to receive vepdegestrant at a dose of 200 mg orally once every day of each 28-day cycle or fulvestrant at a dose of 500 mg, administered intramuscularly, on day 1 and day 15 of cycle 1 and on day 1 of subsequent cycles, with randomization stratified according to ESR1-mutation status and presence or absence of visceral disease. The primary end point was progression-free survival as assessed by blinded independent central review among the patients with ESR1 mutations and among all the patients who underwent randomization. Progression-free survival was estimated with Kaplan-Meier methods and hazard ratios with a stratified Cox proportional-hazards model.

RESULTS:

A total of 624 patients underwent randomization; 313 were assigned to receive vepdegestrant, and 311 to receive fulvestrant. Among the 270 patients with ESR1 mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P<0.001). Among all the patients, the median progression-free survival was 3.8 months (95% CI, 3.7 to 5.3) with vepdegestrant and 3.6 months (95% CI, 2.6 to 4.0) with fulvestrant (hazard ratio, 0.83 [95% CI, 0.69 to 1.01]; P = 0.07). Adverse events of grade 3 or higher occurred in 23.4% of the patients in the vepdegestrant group and in 17.6% of the patients in the fulvestrant group. Adverse events led to treatment discontinuation in 2.9% and 0.7% of the patients, respectively.

CONCLUSIONS:

Among patients with ER-positive, HER2-negative advanced breast cancer, vepdegestrant was associated with significantly longer progression-free survival than fulvestrant in the subgroup with ESR1 mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.).

115

News (Medical) associated with Vepdegestrant

09 Jul 2025

·endpoints.news

Q&A: Retiring Arvinas CEO John Houston talks PROTACs, investor confidence and what’s next with Pfizer

Arvinas CEO John Houston is planning to retire after more than eight years at the helm, the company announced Wednesday, as its lead protein degrader program approaches an inflection point. Arvinas has been on a roller coaster during that time. Houston took the biotech and its targeted protein degraders public, with the promise that the platform — colloquially shortened to PROTACs — could help usher in a wave of new drugs in immuno-oncology and neuroscience. Houston engineered a partnership with Pfizer in 2021, getting $1 billion upfront in cash and equity for Arvinas, and a smaller deal with Novartis last year. More recently, Arvinas has run into some headwinds. The company’s lead PROTAC program, vepdegestrant, disappointed Wall Street in March after a Phase 3 readout, sending its stock price $ARVN down about 50% at the time (Arvinas shares are down 71% in the last 12 months). In May, Pfizer and Arvinas said they would scrap plans for two other Phase 3 studies of vepdegestrant. And at the Jefferies Global Healthcare Conference last month, Houston said Arvinas could end up getting the program’s full rights back. Endpoints News sat down with Houston on Wednesday morning over Zoom to discuss his retirement, the challenges a new CEO will face, and the future of Arvinas. This interview has been edited for length and clarity. Max Gelman: Thanks for taking the time today, John. Why don’t we start on a broad level: Why was now the right time to retire? John Houston: Oh, I’m really old. [Both laugh] I had a significant birthday last year, and certainly the debate and discussion within my family increased a notch in terms of thinking about retirement. I have two younger brothers who are in Scotland, and they both retired a couple of years ago. So I got a lot of stick from them about still working. But for the last year, to be honest, I had been talking to the board about timing and potential transition. We had a lot of really significant data that was coming up at the beginning of the year, pivotal data for vepdegestrant. I didn’t think, and the board didn’t think, that would be an appropriate time to retire prior to that data coming out. Gelman: Where do you see Arvinas now compared to when you started? Houston: When I joined, it was a preclinical company, a private company. And over the last several years, we’ve built really a strong validation of the technology platform to such an extent that there’s now a significant industry all just focused on protein degradation. To be able to stay in the leading wave of a technology is pretty remarkable. We’re in a good cash position as well, with a runway into the tail end of 2028. The only issue we have right now is the stock market not recognizing the value, and that will be part of the challenge for the new CEO coming in: to show how Arvinas’ profile gets recognized externally. Gelman: How can a new CEO try to get the confidence of Wall Street back? Houston: Even though we got the first-ever positive pivotal data for a PROTAC, the stock market reacted as though it was a failure — even though it was actually a positive trial, which was galling. But it is what it is. That’s now seen as a potential overhang to our stock price, which is, “What are you doing with vepdegestrant?” We clearly have to clarify that significantly. The other thing is being smart with capital, and it’s in these situations always a good thing to be able to reduce your burn rate and look towards possibly extending your runway even further, and so that’s been our focus. Those two things in their own right should be a positive step forward in terms of value recognition. Gelman: I want to touch on your comments at the Jefferies conference a few weeks ago, where you were talking about the Pfizer partnership and vepdegestrant. You mentioned that for vepdegestrant, “there’s not as much value as we initially thought, either for us or for Pfizer.” What do you see as the future for this program? Houston: We had pivotal data, but the view was, we didn’t hit on the [intent-to-treat] population, so that was a big negative, even though our base case position was what we delivered. Enough was seen for Pfizer that they did not want to go forward with the first-line study, and they didn’t want to go forward with the second-line study. As soon as they made that decision, the potential value of vepdegestrant on its own became much, much less. So the obvious thing would be for both companies to get together and say, rather than splitting 50-50 profits on a small asset, is there a way of one company getting more of the economics? It could be Pfizer, it could be us. Gelman: How are those discussions with Pfizer going? Do you expect there to be a resolution in terms of potentially changing the collaboration? Houston: The discussions we have with Pfizer are always good. They’re good collaborators. I think they recognize the situation just as well as we do, and they want clarity. They’re good, honest brokers in discussion, so I’ve got a strong, positive feeling that we’ll get to a resolution. And both Pfizer and us know that and want to do that as quickly as possible. Gelman: With a new CEO coming in, will there be any other restructurings or cost-cutting measures? Houston: As I said earlier, there’s two components to driving value for Arvinas. One is getting the vepdegestrant overhang resolved, and the other is making sure that we are doing the right things to be using our capital efficiently. That usually involves some kind of restructuring, but there’s no current plan in the books to do that today. The levers are there for us to pull, and other companies, unfortunately, don’t have levers in these situations. We have a significant portfolio of different programs that we can partner, and the ability to use capital even more effectively. So we’re looking at all aspects of that. Gelman: Just so I’m crystal clear on this, you’re not ruling out a potential restructuring? Houston: Well, I don’t think any company rules out those things. That’s the nature of the business, where the biotech world, for the last few years, has been the upside-down world. Every company is having to do what they have to do to survive. And even at Arvinas, which is in a very strong financial position, we’re cognizant of the fact that investors want to know, how are you using your money effectively, and how are you driving value? Gelman: Thanks for the time, John. Is there anything else you wanted to add? Houston: I’m extremely happy with the last eight and a half years. Once we get through this hiatus with the investors, I think we’ll be back on track. And I look forward to helping find a new CEO and then continuing as the chair of the company. It won’t be quite as intensive as the CEO role, and so I think my wife and family will be happy with that as well.

Phase 3Executive Change

11 Jun 2025

·www.globenewswire.com

Arvinas to Present Preclinical Data for PROTAC BCL6 Degrader, ARV-393, at the 2025 European Hematology Association (EHA) Annual Meeting

– Company to showcase preclinical studies of ARV-393, an investigational oral PROTAC BCL6 degrader, as a single agent in models of nodal T-follicular helper cell lymphoma, angioimmunoblastic-type (AITL) and transformed follicular lymphoma, and in combination with small molecule inhibitors in models of diffuse large B-cell lymphoma – June 05, 2025 -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company working to develop a new class of drugs based on targeted protein degradation, today announced that new preclinical data for ARV-393 will be presented at the European Hematology Association (EHA) meeting, June 12-15, 2025 in Milan, Italy. ARV-393 is Arvinas’ investigational orally bioavailable PROteolysis TArgeting Chimera (PROTAC) degrader targeting the B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. Poster Title: ARV-393, a PROteolysis TArgeting Chimera (PROTAC) BCL6 Degrader, is Efficacious in Preclinical Models of Diffuse Large B-Cell Lymphoma, Nodal T-Follicular Helper Cell Lymphoma, and Transformed Follicular Lymphoma Abstract: PF1000 Session Title: Lymphoma biology & translational research Date: Thursday, June 13, 2025 Time: 6:30-7:30 p.m. CEST ARV-393 is an investigational orally bioavailable PROteolysis TArgeting Chimera (PROTAC) designed to degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. The BCL6 protein facilitates B cell tolerance of rapid proliferation and somatic gene recombination via repressing cell cycle checkpoints, terminal differentiation, apoptosis, and the DNA damage response. PROTAC-mediated degradation has the potential to address the traditional undruggable nature of BCL6. ARV-393 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed/refractory non-Hodgkin lymphoma. Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC protein degrader platform, Arvinas is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. The content above comes from the network. if any infringement, please contact us to modify.

PROTACs

06 Jun 2025

·pipelinereview.com

Arvinas Announces Submission of New Drug Application to U.S. FDA for Vepdegestrant for Patients with ESR1-Mutated ER+/HER2- Advanced or Metastatic Breast Cancer

– This submission is supported by the pivotal Phase 3 VERITAC-2 clinical trial, results of which were recently presented at the 2025 American Society for Clinical Oncology Annual Meeting and published in The New England Journal of Medicine – – VERITAC-2 data support vepdegestrant as a potential treatment option in patients with ESR1m ER+/HER2- advanced or metastatic breast cancer – NEW HAVEN, CT, USA I June 06, 2025 I Arvinas, Inc. (Nasdaq: ARVN), today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) with its partner Pfizer Inc. (NYSE: PFE), for vepdegestrant for the treatment of patients with ER-positive (ER+)/human epidermal growth factor receptor 2 (HER2)-negative (ER+/HER2-) ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy. This submission is based on results from VERITAC-2 (NCT05654623), a global, randomized Phase 3 trial evaluating vepdegestrant versus fulvestrant. “This milestone comes after an exciting presentation at the American Society of Clinical Oncology’s annual meeting,” said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. “We look forward to the NDA review and to the first ever FDA-approved PROTAC ER degrader potentially being available to patients who could benefit from a much needed, new treatment option.” Vepdegestrant is being jointly developed by Arvinas and Pfizer for the treatment of patients with advanced or metastatic ER+/HER2- breast cancer and was granted fast track designation as a monotherapy by the FDA . Results from the VERITAC-2 study were recently presented in a late-breaking oral presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting and were selected for the ASCO press briefing and for Best of ASCO. Detailed results were also simultaneously published in the New England Journal of Medicine . About the VERITAC-2 Clinical Trial The Phase 3 VERITAC-2 clinical trial ( NCT05654623 ) is a global, randomized trial evaluating the efficacy and safety of vepdegestrant (ARV-471) as a monotherapy compared to fulvestrant in patients with ER+/HER2- advanced or metastatic breast cancer. The trial enrolled 624 patients at sites in 25 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy. Patients were randomized 1:1 to receive either vepdegestrant once daily, orally on a 28-day continuous dosing schedule, or fulvestrant, administered intramuscularly on Days 1 and 15 of Cycle 1 and then on Day 1 of each 28-day cycle starting from Day 1 of Cycle 2. In the trial, 43% of patients (n=270) had ESR1 mutations detected. The primary endpoint was progression-free survival (PFS) in the ESR1-mutation and intent-to-treat populations as determined by blinded independent central review. Overall survival is the key secondary endpoint. About Vepdegestrant Vepdegestrant is an investigational, orally bioavailable PROTAC (PROteolysis TArgeting Chimera) protein degrader designed to specifically target and degrade the estrogen receptor (ER). Vepdegestrant is being developed as a potential monotherapy for ER+/HER2- advanced or metastatic breast cancer with estrogen receptor 1 (ESR1) mutations in the second line-plus setting. In July 2021, Arvinas announced a global collaboration with Pfizer for the co-development and co-commercialization of vepdegestrant; Arvinas and Pfizer will share worldwide development costs, commercialization expenses, and profits. The U.S. Food and Drug Administration (FDA) has granted vepdegestrant Fast Track designation as a monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy. About Arvinas Arvinas (Nasdaq: ARVN) is a clinical-stage biotechnology company dedicated to improving the lives of patients suffering from debilitating and life-threatening diseases. Through its PROTAC (PROteolysis TArgeting Chimera) protein degrader platform, the Company is pioneering the development of protein degradation therapies designed to harness the body’s natural protein disposal system to selectively and efficiently degrade and remove disease-causing proteins. Arvinas is currently progressing multiple investigational drugs through clinical development programs, including vepdegestrant, targeting the estrogen receptor for patients with locally advanced or metastatic ER+/HER2- breast cancer; ARV-393, targeting BCL6 for relapsed/refractory non-Hodgkin Lymphoma; and ARV-102, targeting LRRK2 for neurodegenerative disorders. Arvinas is headquartered in New Haven, Connecticut. For more information about Arvinas, visit www.arvinas.com and connect on LinkedIn and X . SOURCE: Arvinas

Phase 3Clinical ResultFast TrackASCO

100 Deals associated with Vepdegestrant

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
ER-positive/HER2-negative/ ESR1-mutated breast cancer	NDA/BLA	United States	Arvinas, Inc.	06 Jun 2025
ER-positive/HER2-negative Breast Cancer	Phase 3	United States	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	United States	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	China	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	China	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	Japan	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	Japan	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	Argentina	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	Argentina	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	Australia	Arvinas Estrogen Receptor, Inc.	03 Mar 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05654623 (VERITAC-2, Pubmed \| N Engl J Med)	Phase 3	Advanced breast cancer	624	Vepdegestrant 200 mg	hzkoconxbd(qcizslcmwp) = in 2.9% and 0.7% of the patients, respectively ljmobirapj (pbxdiivvik ) View more	Positive	31 May 2025
				Fulvestrant 500 mg
NCT05654623 (VERITAC-2, ASCO2025 \| Company_Website) Manual	Phase 3	ER-positive/HER2-negative Breast Cancer ER Positive \| HER2 Negative	624	Vepdegestrant	xdyqgekqfv(dgrrntigto) = rvisbmlgfv rzyfoblpbi (bnzcgwsvnq, 3.6–5.3) View more	Positive	30 May 2025
				fulvestrant	xdyqgekqfv(dgrrntigto) = myynnklmpi rzyfoblpbi (bnzcgwsvnq, 2.2–3.8) View more
NCT05654623 (VERITAC-2, Company_Website) Manual	Phase 3	ER-positive/HER2-negative Breast Cancer ESR1 Mutation	-	Vepdegestrant (ESR1 mutant)	hbftybzjnk(oerhwuhkcb) = The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population. nzfdfctqsm (nzruasgamg )	Negative	11 Mar 2025
				fulvestrant (ESR1 mutant)
NCT05548127 (TACTIVE-U, GlobeNewswire) Manual	Phase 1	ER-positive/HER2-negative Breast Cancer Third line	16	Vepdegestrant + Abemaciclib	rxauxkbzsk(rpqekktesc) = None sgjfimadwk (kqzcllyniq ) View more	Positive	10 Dec 2024
				Vepdegestrant + Abemaciclib (mutant ESR1)
NCT05463952 (Pubmed \| Int J Clin Oncol)	Phase 1	Locally Advanced Unresectable Breast Carcinoma \| Breast Cancer \| Estrogen receptor positive breast cancer ... estrogen receptor (ER) View more	6	Vepdegestrant 200 mg QD	szanjbjdaj(rzgxfbmfgw) = Four (66.7%) patients experienced adverse events; none led to dose reduction or discontinuation rwjaytyrgp (cxxjxmcxgn ) View more	-	20 Nov 2024
NCT05463952 (CTgov)	Phase 1	Locally Advanced Unresectable Breast Carcinoma \| Breast Cancer \| Estrogen receptor positive breast cancer ... View more	6	ARV-471	twoyllmqij = xojxmhqqws jamfozkbug (mohyhhfwyb, ffbkehijtn - mjwxflnegs) View more	-	23 Sep 2024
NCT05538312 (CTgov)	Phase 1	-	12	ARV-471 (Period 1: ARV-471 200 mg)	roguqqidnp(aztlafzeil) = zrkhvwydxc acgfoqygfc (nirgrnnmht, 23) View more	-	23 Sep 2024
				Itraconazole+ARV-471 (Period 2: ARV-471 200 mg + Itraconazole 200 mg)	roguqqidnp(aztlafzeil) = jfbkdwngey acgfoqygfc (nirgrnnmht, 24) View more
NCT05673889 (CTgov)	Phase 1	-	24	Dabigatran (Period 1: Dabigatran 75 mg)	uwvsybaqmg(ulkmtpmcda) = rugevwwlzp vwuoycejbi (aqojptocgw, 94) View more	-	16 Aug 2024
				ARV-471+Dabigatran (Period 2: Dabigatran 75 mg + ARV-471 200 mg)	uwvsybaqmg(ulkmtpmcda) = qyipydwghh vwuoycejbi (aqojptocgw, 66) View more
NCT05652660 (CTgov)	Phase 1	-	12	Rosuvastatin (Period 1: Rosuvastatin)	ughwhxllii(jcpyzutxhy) = hidilbxluu stqqhrtqxz (gauzdisjgh, 53) View more	-	26 Jul 2024
				Rosuvastatin+ARV-471 (Period 2: ARV-471 + Rosuvastatin)	ughwhxllii(jcpyzutxhy) = ucfiynmxks stqqhrtqxz (gauzdisjgh, 48) View more
NCT04072952 (ESMO_BC2024) Manual	Phase 1	ER-positive/HER2-negative Breast Cancer HER2 Negative \| ER Positive \| ESR1 Mutation	46	Vepdegestrant+palbociclib (Total)	emtbqiqgot(soytawsadz) = ≥10% to either vepdegestrant or palbo were neutropenia (91%) and decreased white blood cell count (15%). unhjmsfwdp (dladvaskkc )	Positive	16 May 2024
				Vepdegestrant+palbociclib (Mutant ESR1)

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