[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

/ RecruitingPhase 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]

NCT06347861

/ CompletedPhase 1

A PHASE 1, RANDOMIZED, OPEN-LABEL, 3-PERIOD, 3-TREATMENT, 6-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY IN HEALTHY ADULT PARTICIPANTS TO ESTIMATE THE BIOAVAILABILITY OF THE REGISTRATION TABLETS OF VEPDEGESTRANT (ARV-471, PF-07850327) RELATIVE TO THE PHASE 3 TABLETS

The purpose of the study is to look at how various tablets of a study medicine called vepdegestrant are processed in the body. This will be studied in healthy adult participants after food.
This study looks at how the medicine is changed and removed from the body after a participant takes it.
This study is seeking for participant who:
* are healthy males, and healthy females who do not have the possibility to have children.
* are 18 years of age or older.
* weigh more than 45 Kilograms (99 pounds).
The study consists of 3 treatments. Each participant will be assigned by chance to receive the 3 treatments in a certain sequence. This will be done over 3 study periods. Each treatment consists of a single amount of vepdegestrant taken by mouth in each study period. There will be a washout period between each study periods. The washout period is the time allowed for the medicine to get washed out from the body. How the medicine was processed will be calculated following each dose in each period. The total study duration is about 13 weeks.

Start Date02 Apr 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 Jan 2025·International Journal of Clinical Oncology

Safety and pharmacokinetics of vepdegestrant in Japanese patients with ER+ advanced breast cancer: a phase 1 study

Article

Author: Yoshimura, Akiyo ; Aizawa, Mana ; Yonemori, Kan ; Iwata, Hiroji ; Yoshimitsu, Junichiro ; Mori, Yuko ; Hattori, Masaya ; Umeyama, Yoshiko ; Naito, Yoichi ; Mukohara, Toru

AbstractBackgroundVepdegestrant (ARV-471) is an oral PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader.MethodsThis phase 1 study (NCT05463952) investigated safety, pharmacokinetics, and antitumor activity of vepdegestrant in Japanese patients with ER-positive (ER+)/human epidermal growth factor receptor 2–negative (HER2-) advanced breast cancer at the 200-mg once daily (QD) recommended phase 3 dose. Eligible patients had ER+/HER2- advanced breast cancer resistant to standard therapy, with no standard therapy available, or had received two or more prior endocrine therapies in any setting. The primary endpoint was dose-limiting toxicities (DLTs) in cycle 1; secondary endpoints included safety, pharmacokinetics, and antitumor activity.ResultsSix female patients (median age, 58 [range: 47–62] years) were treated. For advanced disease, three (50.0%) patients received three or more prior regimens and five (83.3%) patients received prior cyclin-dependent kinase 4/6 inhibitors. At data cutoff, median treatment duration was 9.8 (range: 6–28) weeks; two patients remained on treatment. No DLTs were observed. Four (66.7%) patients experienced adverse events; none led to dose reduction or discontinuation. Four (66.7%) patients had treatment-related adverse events; all were grade 1 except anemia (grade 2). Geometric mean maximum plasma concentration and 24-h area under the plasma concentration–time curve of vepdegestrant were 630.9 ng/mL and 10,400 ng∙hr/mL after a single dose and 1056 ng/mL and 18,310 ng∙hr/mL after multiple doses. Two (33.3%) patients demonstrated stable disease at week 24.ConclusionVepdegestrant 200 mg QD was well tolerated in Japanese patients with ER+/HER2- advanced breast cancer with no notable differences in pharmacokinetics from Western patients.Clinical trial registrationClinicalTrials.gov: NCT05463952 (date of registration: July 19, 2022).

12 Dec 2024·Journal of Medicinal Chemistry

Discovery of ERD-12310A as an Exceptionally Potent and Orally Efficacious PROTAC Degrader of Estrogen Receptor α (ERα)

Article

Author: Nishimura, Leticia S ; Priestley, E. Scott ; Carlson, Kathryn ; Rae, James M. ; Acharyya, Ranjan Kumar ; Wang, Meilin ; Gersch, Christina L. ; Rej, Rohan Kalyan ; Wang, Shaomeng ; Wu, Dimin ; Hu, Biao ; Metwally, Hoda ; Wang, Yu ; Wu, Wenxue ; Katzenellenbogen, John A. ; Jiang, Wei ; Xu, Guozhang ; Sui, Zhihua ; Wen, Bo ; Zhang, Weihong ; Bai, Longchuan ; Sun, Duxin ; McEachern, Donna ; Chen, Zhixiang

Inhibition of estrogen receptor alpha (ERα) signaling is an established therapeutic approach for the treatment of ER-positive (ER+) breast cancers, but new therapeutic strategies are urgently needed to overcome clinical resistance. In the present study, we describe the discovery and extensive evaluation of ERD-12310A as an exceptionally potent and orally efficacious PROTAC degrader of ERα. ERD-12310A achieved a DC₅₀ value of 47 pM and is 10 times more potent than ARV-471. ERD-12310A displayed an improved pharmacokinetic profile in mice and rats over ARV-471. ERD-12310A attained tumor regression in the ER+, estrogen-dependent MCF-7 breast cancer xenograft model with wild-type ER and is more potent than ARV-471. Importantly, ERD-12310A achieved strong tumor growth inhibition in MCF-7 xenograft tumors harboring the clinically relevant ESR1^Y537S mutation, which confers resistance to traditional antiestrogens. Our data position ERD-12310A as a promising candidate for further development as a potential therapy for ER+ breast cancer.

10 Oct 2024·Future Oncology

VERITAC-2: a Phase III study of vepdegestrant, a PROTAC ER degrader, versus fulvestrant in ER+/HER2- advanced breast cancer

Article

Author: Wander, Seth A ; Liu, Yuan ; Lu, Dongrui R ; Iwata, Hiroji ; Ma, Cynthia ; Danso, Michael ; Hamilton, Erika P ; Perkins Smith, Julia ; Smith, Julia Perkins ; Campone, Mario ; Laurentiis, Michelino De ; De Laurentiis, Michelino ; Hurvitz, Sara A ; Tran, Lana ; Anderson, Sibyl

Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds an E3 ubiquitin ligase and ER to directly trigger ubiquitination of ER and its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients with ER+/HER2- advanced breast cancer. The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast cancer after treatment with a CDK4/6 inhibitor plus endocrine therapy. Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and ESR1 mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers.Clinical trial registration: NCT05654623 (ClinicalTrials.gov).

News (Medical) associated with Vepdegestrant

10 Jan 2025

·www.globenewswire.com

Arvinas Updates Guidance for First- and Second-Line Phase 3 Combination Trials with Vepdegestrant, Highlights Upcoming Milestones, and Provides Corporate Update

– Vepdegestrant to be combined with Pfizer’s novel investigational CDK4 inhibitor atirmociclib in a first-line Phase 3 trial planned to initiate in 2025; a second-line Phase 3 combination trial will combine vepdegestrant with a CDK4/6 inhibitor, also planned to initiate in 2025 – – Topline data from the monotherapy Phase 3 VERITAC-2 trial of vepdegestrant anticipated in 1Q25 – – The Company recently initiated a Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease – – Data disclosures anticipated from multiple clinical and pre-clinical programs, including ARV-102 and ARV-393, and planned IND submission for a PROTAC KRAS G12D degrader in 2025 – NEW HAVEN, Conn., Jan. 10, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, today announced updated guidance for the planned first- and second-line combination clinical trials for vepdegestrant in patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer, highlighted key upcoming milestones and provided a corporate update. “We are on the cusp of a major transformation in 2025, with the potential to provide significant benefit to patients and meaningful value to our stockholders,” said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. “We are on track to report topline results from our first Phase 3 trial in the first quarter and to initiate two additional Phase 3 trials by the end of the year. In the first half of 2025, we plan to present the first-in-human data from ARV-102, our PROTAC LRRK2 degrader, which we believe will highlight the potential value that our PROTAC degraders may offer for patients with neurodegenerative diseases. And finally, we plan to share initial data from our Phase 1 trial with ARV-393, our PROTAC BCL6 degrader, which will provide an early look the tolerability and efficacy in patients with B-cell lymphomas.” Select milestones anticipated in 2025 Vepdegestrant: Oral PROTAC ER degrader As part of Arvinas’ global collaboration with Pfizer, in 2025 the companies plan to: Announce topline data for the VERITAC-2 Phase 3 monotherapy clinical trial in patients with second-line-plus ER+/HER2- metastatic breast cancer (mBC) (1Q25).Initiate two new Phase 3 combination trials in patients with ER+/HER2- mBC (pending emerging data and regulatory feedback): First-line Phase 3 combination trial with Pfizer’s novel investigational CDK4 inhibitor, atirmociclib.Second-line Phase 3 combination trial with a CDK4/6 inhibitor. With the prioritization of the vepdegestrant plus atirmociclib combination for the first-line setting, the VERITAC-3 trial evaluating vepdegestrant plus palbociclib in the first-line will not proceed beyond the study lead-in. ARV-102: Oral PROTAC LRRK2 degrader Present single-ascending dose data from the ongoing Phase 1 clinical trial in healthy volunteers in an oral session at the Alzheimer’s Disease/Parkinson’s Disease (AD/PD) conference in Vienna, Austria (April 1-4, 2025).Complete enrollment and present initial data from the ongoing Phase 1 clinical trial in patients with Parkinson’s disease. ARV-393: Oral PROTAC BCL6 degrader Present initial data from the ongoing Phase 1 clinical trial in patients with B-cell lymphomas (NCT06393738). Novel PROTAC KRAS G12D degrader File an Investigational New Drug (IND) application. Corporate updateAlex Santini, Arvinas’ Senior Vice President, Global and U.S. Market Access, has been appointed interim Chief Commercial Officer, effective January 17, 2025. Mr. Santini joined Arvinas in 2023 with more than 30 years of experience managing and leading commercial organizations. Previously, he was Executive Vice President, Chief Commercial Officer, at Lexicon Pharmaceuticals. Prior to Lexicon, Mr. Santini was Executive Vice President, U.S. Market Access at Bayer, where he served on the U.S. Executive Committee. Mr. Santini’s prior experience also includes serving as Senior Vice President, Market Access at Nektar Therapeutics, and he began his career at Berlex Laboratories, where he served in roles of increasing responsibility in the commercial organization. John Northcott, Chief Commercial Officer, is leaving the Company for personal reasons, effective January 17, 2025. “Our commercial organization couldn’t be in a better position, and I look forward to working closely with Alex,” continued Dr. Houston. “He has been a highly valued member of the Arvinas team for multiple years, and his well-established ability to build and lead an outstanding commercial team will be invaluable as we prepare for our potential first launch alongside our partners at Pfizer. We thank John for his contributions to the business, particularly his efforts to begin building a strong commercial organization for launch.” About VepdegestrantVepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer. 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- locally advanced or metastatic breast cancer previously treated with endocrine-based therapy. About ArvinasArvinas (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. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995 that involve substantial risks and uncertainties, including statements regarding the plans and expected timing of initiation of two Phase 3 vepdegestrant combination clinical trials, in the first- and second-line settings, pending emerging data and regulatory feedback; the expected timing to report topline data from the VERITAC-2 Phase 3 monotherapy clinical trial of vepdegestrant; the potential to provide significant benefit to patients and meaningful value to stockholders in 2025; the plans and timing of presentation of first-in-human data from ARV-102 and the company’s belief that such data will highlight the potential value that its PROTAC degraders may offer patients with neurodegenerative diseases; the plans and timing of sharing initial data from the company’s Phase 1 clinical trial of ARV-393; and the plans and expected timing of filing an investigational new drug application for a PROTAC KRAS G12D degrader. All statements, other than statements of historical fact, contained in this press release, including statements regarding Arvinas’ strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “goal,” “potential,” “will,” “would,” “could,” “should,” “continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Arvinas may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on such forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements Arvinas makes as a result of various risks and uncertainties, including but not limited to: Arvinas’ and Pfizer’s performance of the respective obligations with respect to Arvinas’ collaboration with Pfizer; whether Arvinas and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant; whether Arvinas will be able to successfully conduct and complete development for its other product candidates, including whether Arvinas initiates and completes clinical trials for its product candidates and receives results from its clinical trials on its expected timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; whether Arvinas’ cash and cash equivalent resources will be sufficient to fund its foreseeable and unforeseeable operating expenses and capital expenditure requirements, and other important factors discussed in the “Risk Factors” section of Arvinas’ Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent other reports, including its quarterly reports, on file with the U.S. Securities and Exchange Commission. The forward-looking statements contained in this press release reflect Arvinas’ current views with respect to future events, and Arvinas assumes no obligation to update any forward-looking statements, except as required by applicable law. These forward-looking statements should not be relied upon as representing Arvinas’ views as of any date subsequent to the date of this release. ContactsInvestors:Jeff Boyle+1 (347) 247-5089Jeff.Boyle@arvinas.com Media:Kirsten Owens+1 (203) 584-0307Kirsten.Owens@arvinas.com

Phase 1Phase 3Executive ChangeFast TrackPROTACs

08 Jan 2025

·www.prnewswire.com

Clarivate Identifies Eleven Potential Blockbuster and Transformative Drugs in Annual Drugs to Watch Report

Anticipated advancements in obesity, oncology, gene therapy and other areas poised to revolutionize patient care LONDON, Jan. 8, 2025 /PRNewswire/ -- Clarivate Plc (NYSE:CLVT) a leading global provider of transformative intelligence, today announced the release of the twelfth annual Drugs to Watch™ report, a trusted guide to the therapies poised to redefine the future of healthcare. This year, the highly anticipated resource highlights 11 drugs projected to achieve blockbuster status or revolutionize treatment paradigms within five years. Since its inception, Drugs to Watch has identified over 98 transformative therapies, cementing its role as an essential resource for navigating the ever-evolving pharmaceutical landscape. This year's report, powered by insights from the Clarivate Cortellis intelligence suite of products, highlights 11 therapies that have recently launched or are set to debut in 2025. These innovations, addressing critical challenges in areas such as obesity, oncology, and gene therapy, are forecast to achieve blockbuster sales by 2030 or dramatically improve patient outcomes on a global scale. The report also explores pivotal trends shaping the industry, including the surging demand for obesity treatments, the transformative potential of gene editing, and the growing impact of regulatory innovation. The report offers an in-depth analysis of the chronic disease market in Mainland China, spotlighting five therapies expected to exceed $1 billion in annual sales over the next five years or deliver transformative outcomes for patients. It also explores critical topics shaping global healthcare, including regulatory advancements, the role of radiopharmaceutical theranostics in oncology, and the growing use of real-world data (RWD) and patient-reported outcomes (PROs) to drive health equity and enhance regulatory submissions. Henry Levy, President, Life Sciences & Healthcare, Clarivate, remarked: "Innovation in the life sciences is reaching unprecedented heights, and this year's Drugs to Watch™ report once again demonstrates the industry's ability to deliver therapies that address unmet medical needs and challenge existing paradigms of care. At Clarivate, we take pride in the precision and reliability of our predictions—last year, we identified 13 molecules as Drugs to Watch, with 12 already approved and launched and one poised for launch. This track record reflects the strength of our comprehensive data and deep expertise. By continuing to provide actionable insights, we empower the sector to navigate opportunities, overcome challenges and drive progress in advancing global health." Mike Ward, Global Head of Thought Leadership, Life Sciences & Healthcare, Clarivate, stated: "2025 represents a turning point for the life sciences sector as it embraces cutting-edge technologies such as AI and machine learning to enhance drug discovery and development. This year's report captures the dynamic forces at play, including groundbreaking progress in precision oncology, the rise of radiopharmaceuticals, and the growing focus on addressing global health disparities." The 2025 Drugs to Watch™ report highlights key trends reshaping the life sciences landscape, emphasizing the transformative impact of emerging technologies and therapeutic breakthroughs. Advances in AI and machine learning are streamlining drug discovery, clinical trials, and real-world data integration, enabling precision medicine approaches. The obesity market is undergoing a revolution driven by next-generation GLP-1 therapies, while radiopharmaceutical theranostics are redefining cancer treatment with a "see it and treat it" paradigm. Gene editing technologies are unlocking new opportunities in personalized medicine, and evolving regulatory frameworks are fostering greater emphasis on patient-reported outcomes and health equity. Together, these trends showcase the sector's resilience and its ability to navigate challenges while driving innovation to improve patient care worldwide. This year's drugs to watch exemplify the fusion of innovation and dedication to advancing patient care in an increasingly complex healthcare ecosystem. The Drugs to Watch™ 2025 list include: AWIQLI® (LAI 287; insulin icodec) developed by Novo Nordisk | Type 1 and type 2 diabetes mellitus AWIQLI®, the first once-weekly, subcutaneous insulin, has launched in Australia, Canada, the EU, Mainland China, and Japan. Its weekly dosing offers a significant advantage over daily basal insulin, potentially reducing the treatment burden for patients with type 1 or type 2 diabetes (T1DM and T2DM). CagriSema (cagrilintide + semaglutide) developed by Novo Nordisk | Obesity and type 2 diabetes mellitus CagriSema, combining cagrilintide, a long-acting amylin analog, with semaglutide, promises superior efficacy over semaglutide (OZEMPIC/WEGOVY®) and tirzepatide (MOUNJARO/ZEPBOUND®) in treating obesity and type 2 diabetes. This next-generation GLP-1 therapy leverages the benefits of GLP-1s, such as enhanced insulin secretion and appetite reduction, while incorporating amylin's effects, including slowed glucose absorption and release. If approved, CagriSema will be the first fixed-dose combination of amylin and GLP-1 receptor agonists in the obesity and T2DM markets. COBENFY™ (KarXT; xanomeline-trospium) developed by Bristol Myers Squibb | Schizophrenia and psychosis related to Alzheimer's disease Amid setbacks for emerging schizophrenia treatments, the approval of COBENFY marks a transformative milestone as the first drug in over 30 years with a novel mechanism of action for treating schizophrenia. Combining xanomeline and trospium, COBENFY selectively targets M1 and M4 receptors, rather than traditional dopamine pathways, while minimizing cholinergic side effects. While further data is needed to assess its effectiveness in Alzheimer's disease-related psychosis, COBENFY shows strong commercial potential if proven effective in treating AD-related hallucinations and delusions. EBGLYSS™ (lebrikizumab) developed by Eli Lilly and Co and Almirall | Atopic dermatitis EBGLYSS™, the third biologic targeting IL-13 for atopic dermatitis, follows DUPIXENT® (dupilumab) and ADBRY®/ADTRALZA® (tralokinumab) to market. Its less frequent dosing, more selective IL-13 inhibition, and strong efficacy and safety data position it as a likely first-line treatment for moderate-to-severe atopic dermatitis when topical corticosteroids are inadequate. Fitusiran developed by Alnylam® Pharmaceuticals Inc and Sanofi | Hemophilia A and B Fitusiran, shown to be effective in phase 3 trials for both hemophilia A and B, regardless of inhibitor status, has the potential to offer a new approach to hemophilia treatment. This small interfering RNA (siRNA) therapy works by inhibiting SerpinPC1 mRNA, reducing antithrombin levels, promoting thrombin generation, and helping to rebalance hemostasis to prevent bleeds. Leveraging Alnylam® Pharmaceuticals' ESC-GalNAc conjugate technology, fitusiran could become the first antithrombin-lowering therapy based on a double-stranded RNA molecule, pending approval. GSK-3536819 (MenABCWY) developed by GSK plc | Meningococcus GSK plc's GSK-3536819 vaccine candidate, a 5-in-1, first-generation formulation, targets the five groups of Neisseria meningitidis (A, B, C, W, and Y) responsible for most invasive meningococcal disease (IMD) cases worldwide. It combines the antigenic components of GSK's licensed meningococcal vaccines, BEXSERO (MenB) and MENVEO (MenACWY), both of which have established efficacy and safety profiles. IMDELLTRA™ (tarlatamab-dlle) developed by Amgen | Small-cell lung cancer (SCLC) IMDELLTRA™ is a first-in-class immunotherapy for extensive-stage small cell lung cancer (ES-SCLC). Using Amgen's bispecific T cell engager (BiTE®) molecules, it targets CD3 on T cells and DLL3 on tumor cells, enabling T cells to attack and lyse the tumor. DLL3 is expressed on the surface of SCLC cells in more than 85% of patients but is minimally expressed on healthy cells making it an attractive target. This mechanism positions IMDELLTRA as a potential standard of care for previously treated ES-SCLC. mRESVIA (mRNA-1345) developed by Moderna Inc | RSV With its U.S. FDA approval in May 2024, mRESVIA® joined AREXVY and ABRYSVO, both featured in Drugs to Watch 2024, as respiratory syncytial virus (RSV) vaccines currently available for adults ages 60 years and older, helping further support the public health initiative to reduce the RSV-related disease burden. Even with available vaccines, RSV infections continue to be a public health concern, particularly for infants and older adults (65 years and older). SEL-212 developed by Sobi® and Cartesian Therapeutics Inc/Selecta Biosciences Inc | Gout SEL-212 is a novel, once-monthly treatment combining pegylated uricase (pegadricase; SEL-037) with ImmTOR™, an immune tolerance technology designed to inhibit the formation of anti-drug antibodies (ADAs). For this application, ImmTOR consists of SEL-110.36, an inhibitor of uricase-specific ADA. This approach may help overcome the limitations of reduced efficacy and tolerability seen with other biologic treatments, such as KRYSTEXXA® (pegloticase), in patients with chronic gout. Vepdegestrant (ARV-471) developed by Arvinas Inc and Pfizer Inc | Breast cancer A global collaboration between Arvinas Inc and Pfizer Inc, vepdegestrant may become the first PROteolysis Targeting Chimera (PROTAC®) protein degrader on the market. Designed to target and degrade the estrogen receptor (ER) protein, early studies suggest PROTAC-induced degradation is more complete than with oral selective estrogen receptor degraders (SERDs). This offers potential for overcoming endocrine resistance in breast cancer. Label expansions, including combination with IBRANCE® (palbociclib), are being explored. Zanzalintinib (XL092) developed by Exelixis Inc | Colorectal cancer, renal cell carcinoma and squamous cell carcinoma of head and neck Zanzalintinib is a third-generation oral tyrosine kinase inhibitor targeting VEGF receptors, MET, and TAM kinases involved in tumor growth and immunosuppression. Currently in phase 3 trials for non-clear-cell renal cell carcinoma (nccRCC), colorectal cancer (CRC) and squamous cell carcinoma of the head and neck (SCCHN), the company anticipates one potential zanzalintinib launch per year starting as early as 2026. Compared to CABOMETYX® (cabozantinib), zanzalintinib may offer benefits, including approval for nccRCC histology and a broader patient population. Access the Drugs to Watch 2025 report from Clarivate, here. For more Drugs to Watch updates and analyses throughout the year, visit the Drugs to Watch web page and follow Clarivate for Life Sciences & Healthcare on LinkedIn and X. Join the conversation, using #DrugstoWatch. To learn more about how Clarivate can help healthcare companies inform and shape the drug discovery, development and delivery process, visit here. Methodology for the Clarivate Drugs to Watch 2025 Report To identify this year's Drugs to Watch, Clarivate drew from the expertise of over 160 analysts covering hundreds of diseases, drugs and markets, along with 11 integrated data sets that span the R&D and commercialization lifecycle, including: Cortellis Competitive Intelligence™, Disease Landscape & Forecast, Epidemiology Intelligence, BioWorld™, Cortellis Regulatory Intelligence™, Drug Timeline & Success Rates, Cortellis Clinical Trials Intelligence™, Cortellis Deals Intelligence™, Access & Reimbursement payer studies, Clarivate Real-World Data and Analytics, Web of Science™, Derwent Innovation™, and other industry sources including biopharma company press releases, filings and peer-reviewed publications. Candidate drugs in phase 2 or phase 3 trials, at pre-registration or registration stage, or already launched in 2024 were selected for analysis, including both novel treatments and already-marketed drugs pursuing new indications that could be particularly impactful. Drugs launched prior to 2024 were excluded. The dataset was filtered for drugs that had total forecast sales of $1 billion or more by 2030. Clarivate experts and analysts evaluated each drug in its individual context, based on factors such as expected approval or launch dates, competitive landscape, regulatory status, trial results, market dynamics and other key factors, and added novel drugs that, while likely to fall short of blockbuster status, are poised to be therapeutic game-changers. Please note that Clarivate analysts generated the data shown in this report prior to December 31, 2024. The Drugs to Watch 2025 Report and the treatments referenced in this release are based on Clarivate's current expectations per existing data, but actual results derived from the drugs named in the report and here may differ significantly. Clarivate is committed to comprehensively supporting customers across the entire drug, device and medical technology lifecycles to advance human health. By combining patient journey data, therapeutic area expertise, artificial intelligence and analytics in ways that unlock hidden insights, data-driven decisions and accelerating innovation, Clarivate's end-to-end research intelligence is designed to enable customers to make informed evidence-based decisions. About Clarivate Clarivate™ is a leading global provider of transformative intelligence. We offer enriched data, insights & analytics, workflow solutions and expert services in the areas of Academia & Government, Intellectual Property and Life Sciences & Healthcare. For more information, please visit . Media Contact: Catherine Daniel Director, External Communications, Life Sciences & Healthcare [email protected] SOURCE Clarivate Plc WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

VaccinePhase 3Immunotherapy

11 Dec 2024

·pipelinereview.com

Arvinas and Pfizer Announce Initial Phase 1b Data from the TACTIVE-U Sub-Study of Vepdegestrant in Combination with Abemaciclib at 2024 San Antonio Breast Cancer Symposium

– Vepdegestrant in combination with abemaciclib demonstrated encouraging clinical activity (clinical benefit rate: 62.5%; overall response rate: 26.7%) in patients previously treated with a CDK4/6 inhibitor – – Safety and tolerability of the combination is generally consistent with the profile of abemaciclib and what has been observed in other clinical trials of vepdegestrant; no significant drug-drug interaction was observed between vepdegestrant and abemaciclib – – Recommended Phase 2 dose identified as 200 mg QD vepdegestrant and 150 mg BID abemaciclib – NEW HAVEN, CT and NEW YORK, NY, USA I December 10, 2024 I Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced preliminary data from the ongoing Phase 1b portion of the TACTIVE-U sub-study of vepdegestrant in combination with abemaciclib among patients with locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. These data will be presented in a poster at the 2024 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas. Preliminary results from 16 patients in the Phase 1b sub-study demonstrated a tolerable safety profile for the combination of abemaciclib 150 mg twice daily (BID) with the recommended Phase 3 monotherapy dose of vepdegestrant (200mg once daily; QD). An encouraging clinical benefit rate of 62.5% was observed among patients with both mutant ESR1 and wild-type ESR1 disease who had all been previously treated with a CDK4/6 inhibitor. Pharmacokinetic data demonstrated no significant drug-drug interaction between vepdegestrant and abemaciclib and no clinically meaningful effect on abemaciclib exposure was observed. In addition to tolerability, the results demonstrated a safety profile consistent with both the known properties of abemaciclib and observed data in other clinical trials for vepdegestrant. These findings support the ongoing Phase 2 portion of the study, which is evaluating full dose abemaciclib (150mg BID) in combination with vepdegestrant (200 mg QD) in post-CDK4/6 advanced breast cancer. “The preliminary results from this Phase 1b sub-study in patients whose cancer had previously progressed after receiving a CDK4/6 inhibitor are encouraging,” said Noah Berkowitz, M.D., Ph.D., Chief Medical Officer at Arvinas. “These data further reinforce our belief that vepdegestrant can be used in multiple combination regimens across the metastatic breast cancer setting and has the potential to become a best-in-class backbone ER therapy. We are pleased to continue in the Phase 2 portion of the study evaluating the standard starting dose of abemaciclib in combination with vepdegestrant.” “With vepdegestrant, we aim to develop a novel agent that has the potential to become a new backbone endocrine therapy in ER+ metastatic breast cancer,” said Roger Dansey, M.D., Chief Development Officer, Oncology, Pfizer. “We are pleased to see these initial results, which complement previously reported data demonstrating the potential of combination therapy with vepdegestrant to address unmet needs for patients.” Additional detail on the TACTIVE-U poster presentation at SABCS follows below: Title: Vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) Estrogen Receptor (ER) Degrader, Plus Abemaciclib in ER-Positive/Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced or Metastatic Breast Cancer: TACTIVE-U Preliminary Phase 1b Results Date: Thursday, December 12, 2024 Time: 5:30 – 7:00 p.m. CDT Poster: P4-12-03 Key findings included in the poster (data cut-off: August 30, 2024): Arvinas and Pfizer are continuing to evaluate data from the ongoing TACTIVE-U clinical trial, which includes combinations of vepdegestrant plus abemaciclib, ribociclib or samuraciclib (ClinicalTrials.gov Identifiers: NCT05548127, NCT05573555, and NCT06125522). About Vepdegestrant Vepdegestrant is an investigational, orally bioavailable PROTAC protein degrader designed to specifically target and degrade the estrogen receptor (ER) for the treatment of patients with ER positive (ER+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Vepdegestrant is being developed as a potential monotherapy and as part of combination therapy across multiple treatment settings for ER+/HER2- metastatic breast cancer. 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- locally 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 . About Pfizer Oncology At Pfizer Oncology, we are at the forefront of a new era in cancer care. Our industry-leading portfolio and extensive pipeline includes three core mechanisms of action to attack cancer from multiple angles, including small molecules, antibody-drug conjugates (ADCs), and bispecific antibodies, including other immune-oncology biologics. We are focused on delivering transformative therapies in some of the world’s most common cancers, including breast cancer, genitourinary cancer, hematology-oncology, and thoracic cancers, which includes lung cancer. Driven by science, we are committed to accelerating breakthroughs to help people with cancer live better and longer lives. About Pfizer: Breakthroughs That Change Patients’ Lives At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development, and manufacture of health care products, including innovative medicines and vaccines. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments, and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments, and local communities to support and expand access to reliable, affordable health care around the world. For 175 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.Pfizer.com . In addition, to learn more, please visit us on www.Pfizer.com and follow us on X at @Pfizer and @Pfizer News , LinkedIn , YouTube and like us on Facebook at Facebook.com/Pfizer . SOURCE: Pfizer

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Indication	Highest Phase	Country/Location	Organization	Date
ER-positive/HER2-negative Breast Cancer	Phase 3	ZA	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	PL	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	AR	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	PL	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	AR	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	CA	Pfizer Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	HU	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	ZA	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	FR	Arvinas Estrogen Receptor, Inc.	03 Mar 2023
ER-positive/HER2-negative Breast Cancer	Phase 3	BR	Pfizer Inc.	03 Mar 2023

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05548127 (TACTIVE-U, GlobeNewswire) Manual	Phase 1	ER-positive/HER2-negative Breast Cancer Third line	16	Vepdegestrant + Abemaciclib	(bxvkwkdzav) = None mzkapafloz (fshqweyler ) View more	Positive	10 Dec 2024
				Vepdegestrant + Abemaciclib (mutant ESR1)
NCT05463952 (Pubmed \| Int J Clin Oncol)	Phase 1	Breast Cancer estrogen receptor (ER)	6	Vepdegestrant 200 mg QD	qrdrpsrryz(bmmmyncxhx) = Four (66.7%) patients experienced adverse events; none led to dose reduction or discontinuation rtkuijsbmg (suyhvlwfhk ) View more	-	20 Nov 2024
NCT05463952 (CTgov)	Phase 1	Breast Cancer	6	ARV-471	xlfwmaqdmr(elchmfmpxw) = xwgelmloqz acxbnbtzko (nnsafsojjn, fupnkdwsog - nynbmrubql) View more	-	23 Sep 2024
NCT05538312 (CTgov)	Phase 1	-	12	ARV-471 (Period 1: ARV-471 200 mg)	vljxrrmqcv(tcztpgsuxy) = tvpohtkyim jrwkdhsqhm (ookewzkbph, kgnasydufs - enkzpalhpq) View more	-	23 Sep 2024
				Itraconazole+ARV-471 (Period 2: ARV-471 200 mg + Itraconazole 200 mg)	vljxrrmqcv(tcztpgsuxy) = iurqwrsxek jrwkdhsqhm (ookewzkbph, tjjihwjhqw - wjegczwfrd) View more
NCT05673889 (CTgov)	Phase 1	-	24	Dabigatran (Period 1: Dabigatran 75 mg)	twycxkpdne(wkumoeqxry) = foymdbimqr fjfewnpuvu (mwmauoxxoa, pruhaefgur - embxmkjboy) View more	-	16 Aug 2024
				ARV-471+Dabigatran (Period 2: Dabigatran 75 mg + ARV-471 200 mg)	twycxkpdne(wkumoeqxry) = gupsqwepmu fjfewnpuvu (mwmauoxxoa, xztqopcvsk - loxzspzxnm) View more
NCT05652660 (CTgov)	Phase 1	-	12	Rosuvastatin (Period 1: Rosuvastatin)	eekwwrflkj(mizirssxna) = kuagqxclqq emddckbumw (tpdyccwemu, floqoclcsk - pfykyvgwvt) View more	-	26 Jul 2024
				Rosuvastatin+ARV-471 (Period 2: ARV-471 + Rosuvastatin)	eekwwrflkj(mizirssxna) = ftinopvtsm emddckbumw (tpdyccwemu, lceedbccib - qjldkjplbq) View more
NCT04072952 (ESMO_BC2024) Manual	Phase 1	ER-positive/HER2-negative Breast Cancer \| \|	46	Vepdegestrant+palbociclib (Total)	(skfkdootda) = ≥10% to either vepdegestrant or palbo were neutropenia (91%) and decreased white blood cell count (15%). jfcdefssug (zenaexckox )	Positive	16 May 2024
				Vepdegestrant+palbociclib (Mutant ESR1)
NCT06206837 (TACTIVE-K, ESMO_BC2024)	Phase 1/2	ER-positive/HER2-negative Breast Cancer ER+ \| HER2-	65	Vepdegestrant	(ubkndyizqz) = ngrawudmjj lwluvuejce (ukhfwdauzk )	-	14 May 2024
NCT04072952 (ESMO2023)	Phase 1/2	ER-positive/HER2-negative Breast Cancer	-	Vepdegestrant	(vdaxxdldvq) = yohkupwzgr nljrrrpncy (rjittmdpon, 26 - 49)	-	21 Oct 2023
NCT04072952 (VERITAC, ESMO_BC2023)	Phase 2	ER-positive/HER2-negative Breast Cancer mutant ESR1	35	ARV-471 200 mg QD	(vbtrmjhszw) = zstocmwyqo xciqwpnlzw (fgyankkano, 21 - 55) View more	Positive	12 May 2023

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