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First-in-human phase I study of ARV-110, an androgen receptor (AR) PROTAC degrader in patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) following enzalutamide (ENZ) and/or abiraterone (ABI).
Abstract
3500 Background: Proteolysis Targeting Chimera (PROTAC) protein degraders induce selective degradation of targeted proteins by engaging the ubiquitin proteasome system. ARV-110 is an orally bioavailable PROTAC that specifically degrades AR ≥ 95% and achieves anti-tumor activity in ENZ-naïve and -resistant prostate cancer xenograft models. Methods: To define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of ARV-110, pts with ≥ 2 prior therapies for mCRPC, including ENZ and/or ABI, received ARV-110 orally once daily. Dose escalation is per 3+3 design. Endpoints include dose limiting toxicities (DLTs), adverse events (AEs), pharmacokinetics (PK), biomarkers (e.g., AR mutation analysis), RECIST and PSA response. Results: By January 2020, 18 pts were dosed: 35 mg (N = 3), 70 mg (N = 4), 140 mg (N = 8), 280 mg (N = 3). 12 pts received both ENZ and ABI; 14 received prior chemotherapy. 1 of 18 pts experienced a DLT (280 mg) of Grade (Gr) 4 elevated AST/ALT followed by acute renal failure while taking rosuvastatin (ROS). A 2 nd pt had Gr 3 AST/ALT with ROS that resolved off ROS, permitting ARV-110 retreatment. ROS plasma concentrations demonstrated significant increases concurrent with AST/ALT elevations in both pts. Subsequently, ROS was prohibited without further ≥Gr 2 AST/ALT AEs. No other related Gr 3/4 AEs were reported. ARV-110 PK was generally dose proportional and at 140 mg reached levels associated with preclinical anti-tumor activity. 15 pts were evaluable for PSA response (excludes 1 pt stopped after 1 dose for early progression and 2 pts initiated 2 weeks before cutoff, all at 140 mg). Of these, 8 pts initiated dosing at ≥140 mg. 2 pts achieved confirmed PSA declines of >50%, both at 140 mg. Prior therapy in both pts included ENZ and ABI, chemotherapy, bicalutamide and radium-223 plus other regimens. 1 pt had 2 AR mutations known to confer ENZ resistance. The 2nd pt also achieved an unconfirmed RECIST partial response (confirmatory scan pending). Both responses were ongoing at data cutoff (8+ and 21+ weeks of treatment). Conclusions: To date, ARV-110 has an acceptable safety profile. Concurrent ROS is now prohibited. MTD has not yet been established; determination of RP2D continues. ARV-110 demonstrates antitumor activity in mCRPC after ENZ/ABI with 2 ongoing confirmed PSA responses, one of which was associated with tumor reduction. Updated data for this first PROTAC in clinical testing will be presented. Clinical trial information: NCT03888612 .
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“Initial trial data showed that ARV-110 was well tolerated at doses up to 420 mg.”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [40]
In the citing paper
“The data also demonstrated ARV-110-mediated degradation of the protein target in tumours — the first such evidence for a PROTAC molecule in humans — and revealed early signs of antitumour activity, as measured by reductions in levels of prostate specific antigen (PSA) and/or by RECIST (Response Evaluation Criteria in Solid Tumors).”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [40]
In the citing paper
“The data also demonstrated ARV-110-mediated degradation of the protein target in tumours — the first such evidence for a PROTAC molecule in humans — and revealed early signs of antitumour activity, as measured by reductions in levels of prostate specific antigen (PSA) and/or by RECIST (Response Evaluation Criteria in Solid Tumors).”
From PROTAC targeted protein degraders: the past is prologue (2022) · cites this paper as [40]
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Items 101–165 of 165
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Wu, B., Koehler, A. N., & Westcott, P. M. K. (2024) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2024.08.002 · Cited by 9
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“Phase I trials of ARV-110 for patients with me mCRPC showed that ARV-110 reduced prostate-specific antigen (PSA) levels by more than 50% in 40% patients, and the biopsy data of one patient showed a 70% ~ 90% decrease in AR [40].”
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Nabet, B. (2020) · ChemBioChem · doi:10.1002/cbic.202000531 · Cited by 8
Yang, X., He, Y., Kim, R. D., Fleming, J. B., & Xie, H. (2020) · Targeted Oncology · doi:10.1007/s11523-020-00782-2 · Cited by 10
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Boyd, S. R., Chang, L., de Rezende, W. C., Raji, I. O., Kandel, P., Holmes, S. L., & Young, D. W. (2020) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2020.140534 · Cited by 7
Sun, Y., Wang, H., Li, Y., Li, Z., Mao, Z., Zhang, M., Shao, Y., Ye, J., Li, D., & Shan, L. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.107309 · Cited by 7
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Anugu, A., Singh, P., Kashyap, D., Jillwin, J., Naik, S., Sarkar, S., Zaman, K., Dhaliwal, M., Nagar, S., Gupta, T., et al. (2025) · Microorganisms · doi:10.3390/microorganisms13071557 · Cited by 5
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Tripathi, A., Chhabra, A., Rizvi, S., & Tyagi, R. K. (2025) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2025.112569 · Cited by 4
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“The final recommended phase 2 dosing was selected to be 420 mg QD [23].”
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Iaxx, R., Teyssonneau, D., Fallaha, C., et al. (2025) · Current Opinion in Urology · doi:10.1097/mou.0000000000001341 · Cited by 3
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Ma, L., & Han, X. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23932-8.00020-0 · Cited by 3
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Kjølbye, L. R., Pereira, G. P., Bartocci, A., et al. (2022) · QRB Discovery · doi:10.1017/qrd.2022.16.pr4
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Kjølbye, L. R., Pereira, G. P., Bartocci, A., et al. (2022) · QRB Discovery · doi:10.1017/qrd.2022.16.pr2
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Guidi, L., Trapani, D., & Curigliano, G. (2025) · Current Opinion in Oncology · doi:10.1097/cco.0000000000001187
Ji, Y., Wu, M. Y., Dong, H., Zhang, R., Chen, H., Mao, H., Han, X., Chen, Z., & Zhou, J. (2025) · The FASEB Journal · doi:10.1096/fj.202403170rr
“A notable example is the PROTAC ARV-110, which effectively inhibits the growth of enzalutamide (ENZa)- resistant tumors through AR degradation [27].”
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Sireen, U., Thota, S., Amreen, N., Kumaraswamy, D., Katherashala, S., & Sriram, S. (2026) · In Silico Research in Biomedicine · doi:10.1016/j.insi.2026.100386
Pandiyan, S., Zhou, M., Chen, Y., Shao, J., Yao, M., & wang, L. (2026) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2026.109449
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Kim, C.-H. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-45844-6.00017-2
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Metadata
- Authors
- Petrylak, D. P., Gao, X., Vogelzang, N. J., Garfield, M. H., Taylor, I., Dougan Moore, M., Peck, R. A., & Burris, H. A.
- Affiliations
- Yale University (US)
- Massachusetts General Hospital (US)
- Comprehensive Cancer Centers of Nevada (US)
- Arvinas (United States) (US)
- Arvinas, Inc, New Haven, CT;
- Sarah Cannon (US)
- Venue
- Journal of Clinical Oncology
- Published
- 2020-05-20
- Volume
- 38
- Issue
- 15_suppl
- Pages
- 3500-3500
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W3031756382
- Cited by
- 169
- References
- 0
- Citations by year
- 2026: 14 · 2025: 24 · 2024: 31 · 2023: 23 · 2022: 38 · 2021: 30 · 2020: 9
- Type
- conference abstract
- Language
- en
- Open access
- closed
- Locations
- Journal of Clinical Oncology (publishedVersion)
- Funders
- Arvinas
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Keywords
- PROTAC degraders, androgen receptor degradation, metastatic castration-resistant prostate cancer, enzalutamide, abiraterone, maximum tolerated dose, dose-limiting toxicity, rosuvastatin, hepatotoxicity, pharmacokinetics, PSA response, androgen receptor mutations, dose escalation, treatment-emergent adverse events
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