Arvinas and Pfizer Announce Positive Topline Results from Phase 3 VERITAC-2 Clinical Trial
Arvinas (ARVN) and Pfizer (PFE) announced positive topline results from their Phase 3 VERITAC-2 clinical trial for vepdegestrant, a first-in-class investigational oral PROTAC ER degrader for breast cancer treatment.
The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, showing statistically significant and clinically meaningful improvement in progression-free survival compared to fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population, though the trial did not reach statistical significance in the intent-to-treat population.
Vepdegestrant was generally well tolerated, with a safety profile consistent with previous studies. Overall survival data was not mature at analysis time, with less than 25% of required events occurred. The FDA granted Fast Track designation for vepdegestrant in February 2024 for monotherapy in ER+/HER2- advanced or metastatic breast cancer patients previously treated with endocrine-based therapy.
Arvinas (ARVN) e Pfizer (PFE) hanno annunciato risultati positivi preliminari dal loro studio clinico di fase 3 VERITAC-2 per vepdegestrant, un degrader PROTAC ER orale di prima classe in fase di sperimentazione per il trattamento del cancro al seno.
Lo studio ha raggiunto il suo obiettivo primario nella popolazione mutante del recettore estrogenico 1 (ESR1m), mostrando un miglioramento statisticamente significativo e clinicamente rilevante nella sopravvivenza libera da progressione rispetto al fulvestrant. I risultati hanno superato il rapporto di rischio target predefinito di 0,60 nella popolazione ESR1m, anche se lo studio non ha raggiunto la significatività statistica nella popolazione intent-to-treat.
Vepdegestrant è stato generalmente ben tollerato, con un profilo di sicurezza coerente con studi precedenti. I dati sulla sopravvivenza globale non erano maturi al momento dell'analisi, con meno del 25% degli eventi richiesti verificatisi. La FDA ha concesso la designazione Fast Track per vepdegestrant nel febbraio 2024 per la monoterapia in pazienti con cancro al seno avanzato o metastatico ER+/HER2- precedentemente trattati con terapia endocrina.
Arvinas (ARVN) y Pfizer (PFE) anunciaron resultados preliminares positivos de su ensayo clínico de fase 3 VERITAC-2 para vepdegestrant, un degradador PROTAC ER oral de primera clase en investigación para el tratamiento del cáncer de mama.
El ensayo cumplió con su objetivo principal en la población mutante del receptor de estrógeno 1 (ESR1m), mostrando una mejora estadísticamente significativa y clínicamente relevante en la supervivencia libre de progresión en comparación con el fulvestrant. Los resultados superaron la razón de riesgo objetivo preespecificada de 0.60 en la población ESR1m, aunque el ensayo no alcanzó significancia estadística en la población intent-to-treat.
Vepdegestrant fue generalmente bien tolerado, con un perfil de seguridad consistente con estudios previos. Los datos de supervivencia global no estaban maduros en el momento del análisis, con menos del 25% de los eventos requeridos ocurridos. La FDA otorgó la designación Fast Track para vepdegestrant en febrero de 2024 para monoterapia en pacientes con cáncer de mama avanzado o metastásico ER+/HER2- que habían sido tratados previamente con terapia endocrina.
Arvinas (ARVN)와 Pfizer (PFE)는 유방암 치료를 위한 최초의 경구 PROTAC ER 분해제인 vepdegestrant에 대한 3상 VERITAC-2 임상 시험의 긍정적인 초기 결과를 발표했습니다.
이 시험은 에스트로겐 수용체 1 변이군(ESR1m) 집단에서 주요 목표를 달성했으며, fulvestrant와 비교하여 진행 없는 생존율에서 통계적으로 유의미하고 임상적으로 중요한 개선을 보여주었습니다. 결과는 ESR1m 집단에서 사전 지정된 목표 위험 비율인 0.60을 초과했지만, 시험은 의도 치료 집단에서는 통계적 유의성을 달성하지 못했습니다.
Vepdegestrant는 일반적으로 잘 견디며, 이전 연구와 일치하는 안전성 프로필을 보였습니다. 분석 시점에서 전체 생존 데이터는 성숙하지 않았으며, 필요한 사건의 25% 미만이 발생했습니다. FDA는 2024년 2월 ER+/HER2- 진행성 또는 전이성 유방암 환자에 대한 단독 요법으로 vepdegestrant에 대해 신속 심사 지정을 부여했습니다.
Arvinas (ARVN) et Pfizer (PFE) ont annoncé des résultats préliminaires positifs de leur essai clinique de phase 3 VERITAC-2 pour vepdegestrant, un dégradateur PROTAC ER oral de première classe en cours d'investigation pour le traitement du cancer du sein.
L'essai a atteint son objectif principal dans la population mutante du récepteur des œstrogènes 1 (ESR1m), montrant une amélioration statistiquement significative et cliniquement pertinente de la survie sans progression par rapport au fulvestrant. Les résultats ont dépassé le ratio de risque cible préspécifié de 0,60 dans la population ESR1m, bien que l'essai n'ait pas atteint de signification statistique dans la population en intention de traiter.
Le vepdegestrant a été généralement bien toléré, avec un profil de sécurité cohérent avec des études antérieures. Les données sur la survie globale n'étaient pas matures au moment de l'analyse, moins de 25 % des événements requis s'étant produits. La FDA a accordé la désignation Fast Track au vepdegestrant en février 2024 pour une monothérapie chez les patients atteints de cancer du sein avancé ou métastatique ER+/HER2- ayant déjà reçu un traitement basé sur des thérapies endocriniennes.
Arvinas (ARVN) und Pfizer (PFE) haben positive vorläufige Ergebnisse aus ihrer Phase-3-Studie VERITAC-2 für vepdegestrant bekannt gegeben, einen erstklassigen oralen PROTAC ER-Degrader zur Behandlung von Brustkrebs.
Die Studie erreichte ihr primäres Ziel in der Population mit dem Mutanten Östrogenrezeptor 1 (ESR1m) und zeigte eine statistisch signifikante und klinisch relevante Verbesserung des progressionsfreien Überlebens im Vergleich zu Fulvestrant. Die Ergebnisse übertrafen das vorab festgelegte Ziel-Hazard-Verhältnis von 0,60 in der ESR1m-Population, obwohl die Studie in der Intention-to-Treat-Population keine statistische Signifikanz erreichte.
Vepdegestrant wurde im Allgemeinen gut vertragen, mit einem Sicherheitsprofil, das mit früheren Studien übereinstimmt. Die Daten zur Gesamtüberlebensrate waren zum Zeitpunkt der Analyse nicht ausgereift, da weniger als 25 % der erforderlichen Ereignisse aufgetreten waren. Die FDA erteilte im Februar 2024 die Fast-Track-Zulassung für Vepdegestrant zur Monotherapie bei ER+/HER2- fortgeschrittenen oder metastasierten Brustkrebspatienten, die zuvor mit einer endokrin basierten Therapie behandelt wurden.
- First PROTAC degrader to show clinical benefit in Phase 3 trial
- Met primary endpoint with significant PFS improvement in ESR1m population
- Exceeded pre-specified target hazard ratio of 0.60
- FDA Fast Track designation received
- Well-tolerated safety profile consistent with previous studies
- Failed to reach statistical significance in intent-to-treat population
- Overall survival data still immature with less than 25% of required events
Insights
Arvinas and Pfizer's announcement of positive Phase 3 VERITAC-2 results represents a breakthrough moment for targeted protein degradation technology in oncology. This marks the first-ever PROTAC degrader to demonstrate clinical benefit in a pivotal trial - a watershed moment for this therapeutic approach.
The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, showing statistically significant and clinically meaningful improvement in progression-free survival versus fulvestrant. The results exceeded the pre-specified target hazard ratio of 0.60, indicating substantial efficacy. While the broader intent-to-treat population didn't reach statistical significance, the ESR1m success is particularly meaningful.
Oncology Specialist: ESR1 mutations occur in approximately 30% of ER+/HER2- metastatic breast cancer patients who progress on endocrine therapy, representing a significant unmet medical need. These mutations drive resistance to standard endocrine therapies like aromatase inhibitors. Vepdegestrant's mechanism - directly degrading the estrogen receptor rather than just blocking it - appears particularly effective against these mutations. The current standard of care, fulvestrant, requires inconvenient intramuscular injections, while vepdegestrant offers the convenience of oral administration with superior efficacy in this mutation-positive population.
Biotechnology Analyst: This result validates Arvinas's entire PROTAC platform technology, potentially unlocking value across their pipeline. For a company with a
– VERITAC-2 achieved its primary endpoint in the estrogen receptor 1-mutant population, demonstrating statistically significant and clinically meaningful improvement in progression-free survival –
– Vepdegestrant is the first PROTAC degrader to demonstrate clinical benefit
in a Phase 3 trial –
NEW HAVEN, Conn. and NEW YORK, March 11, 2025 (GLOBE NEWSWIRE) -- Arvinas, Inc. (Nasdaq: ARVN) and Pfizer Inc. (NYSE: PFE) today announced positive topline results from the Phase 3 VERITAC-2 clinical trial (NCT05654623) evaluating vepdegestrant monotherapy versus fulvestrant in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) advanced or metastatic breast cancer whose disease progressed following prior treatment with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapy. These are the first pivotal data for vepdegestrant, a potential first-in-class investigational oral PROteolysis TArgeting Chimera (PROTAC) ER degrader.
The trial met its primary endpoint in the estrogen receptor 1-mutant (ESR1m) population, demonstrating a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to fulvestrant. 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.
“The first Phase 3 data readout for a PROTAC degrader represents a significant achievement and these data show that vepdegestrant has the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations,” said John Houston, Ph.D., Chairperson, Chief Executive Officer and President at Arvinas. “We want to thank the patients and investigators who participated in this trial, and we look forward to sharing these data with health authorities as well as at a medical conference in 2025.”
Overall survival was not mature at the time of the analysis, with less than a quarter of the required number of events having occurred. The trial will continue to assess overall survival as a key secondary endpoint. In the trial, vepdegestrant was generally well tolerated and its safety profile was consistent with what has been observed in previous studies. Detailed results from VERITAC-2 will be submitted for presentation at a medical meeting later this year, and these data will be shared with global regulatory authorities to potentially support regulatory filings.
“Patients with advanced ER+/HER2- metastatic breast cancer face significant clinical challenges, with limited treatment options following disease progression and the development of resistance to available endocrine therapies,” said Megan O’Meara, M.D., Interim Chief Development Officer, Pfizer Oncology. “These data from VERITAC-2 support the potential of vepdegestrant to give patients whose tumors harbor ESR1 mutations additional time without disease progression, compared to fulvestrant.”
Vepdegestrant is an investigational oral PROTAC ER degrader for ER+/HER2- breast cancer being jointly developed by Arvinas and Pfizer and is designed to harness the body’s natural protein disposal system to specifically target and degrade the ER. In February 2024, the companies announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for the investigation of vepdegestrant for monotherapy in the treatment of adults with ER+/HER2- advanced or metastatic breast cancer previously treated with endocrine-based therapy.
About Metastatic Breast Cancer
About 2.3 million new breast cancer diagnoses were reported globally in 2022,1 and it is estimated there will be nearly 320,000 people diagnosed with breast cancer in the U.S. in 2025.2 Estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer accounts for approximately
Nearly
About the VERITAC-2 Clinical Trial
The Phase 3 VERITAC-2 clinical trial (NCT05654623) is a global randomized study 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 26 countries who had previously received treatment with a CDK4/6 inhibitor plus endocrine therapy.
Patients were randomized 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. The primary endpoint was progression-free survival (PFS) in the intent-to-treat and ESR1m populations as determined by blinded independent central review. Overall survival is a 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) 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- 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.
Arvinas Forward-Looking Statements
This 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: vepdegestrant having the potential to provide clinically meaningful outcomes for thousands of patients with metastatic breast cancer whose tumors harbor estrogen receptor 1 mutations; Arvinas’ and Pfizer’s plans to share data from the Phase 3 VERITAC-2 clinical trial with health authorities, including to potentially support regulatory filings, as well as at a medical conference in 2025; and vepdegestrant’s development as a potential monotherapy and as part of combination therapy across multiple treatment settings for estrogen receptor positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. 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,” “plan,” “target,” “goal,” “potential,” “will,” “would,” “could,” “should,” “look forward,” “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: whether Arvinas and Pfizer will successfully perform their respective obligations under the collaboration between Arvinas and Pfizer; whether Arvinas and Pfizer will be able to successfully conduct and complete clinical development for vepdegestrant as a monotherapy and as part of combination therapy; whether Arvinas will be able to successfully conduct and complete development for its other product candidates, including ARV-393 and ARV-102; whether Arvinas and Pfizer, as appropriate, will be able to obtain marketing approval for and commercialize vepdegestrant and other product candidates on current timelines or at all; Arvinas’ ability to protect its intellectual property portfolio; Arvinas’ reliance on third parties; whether Arvinas will be able to raise capital when needed; 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, 2024 and subsequent other 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.
Pfizer Disclosure Notice:
The information contained in this release is as of March 11, 2025. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.
This release contains forward-looking information about Pfizer Oncology and vepdegestrant, including its potential benefits, vepdegestrant’s potential for adults with ER+/HER2- advanced or metastatic breast cancer whose disease progressed following prior treatment with CDK 4/6 inhibitors and endocrine-based therapy and plans to share these data with global regulatory authorities to potentially support regulatory filings, that involve substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements.
Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; whether the VERITAC-2 trial will meet the secondary endpoint for overall survival; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications may be filed in any jurisdictions for any potential indication for vepdegestrant; whether and when any such applications that may be filed for vepdegestrant may be approved by regulatory authorities, which will depend on myriad factors, including making a determination as to whether the product's benefits outweigh its known risks and determination of the product's efficacy, and, if approved, whether vepdegestrant will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or other matters that could affect the availability or commercial potential of vepdegestrant; whether the collaboration between Pfizer and Arvinas will be successful; uncertainties regarding the impact of COVID-19 on our business, operations and financial results; and competitive developments.
A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2024, and in its subsequent reports on Form 10-Q, including in the sections thereof captioned “Risk Factors” and “Forward-Looking Information and Factors That May Affect Future Results”, as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.
1 World Health Organization. (2024, March 13). Breast cancer. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/breast-cancer
2 Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. doi: 10.3322/caac.21871. Epub 2025 Jan 16. PMID: 39817679; PMCID: PMC11745215.
3 Surveillance, Epidemiology, and End Results Program Data, https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
4 Redig AJ, McAllister SS. Breast cancer as a systemic disease: a view of metastasis. J Intern Med. 2013;274(2):113-126. doi:10.1111/joim.12084.
5 Bidard F-C, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. Journal of Clinical Onoclogy. 2022 May https://doi.org/10.1200/JCO.22.00338.
6 Kalinsky, K. Abemaciclib Plus Fulvestrant in Advanced Breast Cancer After Progression on CDK4/6 Inhibition: Results From the Phase III postMONARCH Trial. Journal of Clinical Oncology. 2024 Dec. https://doi.org/10.1200/JCO-24-0208.
7 Tolaney, S. et al. AMEERA-3: Randomized Phase II Study of Amcenestrant (Oral Selective Estrogen Receptor Degrader) Versus Standard Endocrine Monotherapy in Estrogen Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Advanced Breast Cancer. Journal of Clinical Oncology. https://ascopubs.org/doi/full/10.1200/JCO.22.02746.
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| Arvinas Media Contact: | Kirsten Owens +1 (203) 586-0307 Kirsten.Owens@Arvinas.com |
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FAQ
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