{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:49:29Z","timestamp":1791578969835,"version":"4.3.4"},"reference-count":49,"publisher":"American Society of Clinical Oncology (ASCO)","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>This phase I\/II study (which, to our knowledge, is the first such study in humans) evaluated the safety and efficacy of bavdegalutamide (ARV-110), a proteolysis-targeting chimera (PROTAC) androgen receptor (AR) degrader, in patients with metastatic castration-resistant prostate cancer (mCRPC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      Eligible patients were adult (18 years and older) males with mCRPC previously treated with an AR pathway inhibitor (ARPI). In phase I, patients received escalating doses of oral bavdegalutamide to determine the recommended phase II dose (RP2D). In phase II, patients received bavdegalutamide at the RP2D in 28-day cycles. Antitumor activity, including prostate-specific antigen (PSA) response rate (\u226550% [PSA\n                      <jats:sub>50<\/jats:sub>\n                      ] or \u226530% [PSA\n                      <jats:sub>30<\/jats:sub>\n                      ] decline from baseline) and radiographic progression-free survival (rPFS), was assessed in three AR molecular profile\u2013defined subgroups and a less-pretreated (one prior ARPI without prior chemotherapy) subgroup.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In phase I (N = 95), bavdegalutamide 420 mg once daily was the RP2D. In phase II, PSA\n                      <jats:sub>50<\/jats:sub>\n                      and PSA\n                      <jats:sub>30<\/jats:sub>\n                      rates, respectively, were 60.0% and 70.0% among patients with tumors harboring\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      T878 and\/or H875 mutations (n = 20), 4.3% and 6.5% among those with wild-type\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      or other\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      alterations (n = 46), and 3.1% and 6.3% among those with\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      L702H mutations or AR splice variant 7 expression (n = 32); the median rPFS was 11.1, 4.2, and 5.1 months in the respective subgroups. Among less-pretreated patients (n = 42), the PSA\n                      <jats:sub>50<\/jats:sub>\n                      rate was 21.4%, the PSA\n                      <jats:sub>30<\/jats:sub>\n                      rate was 23.8%, and the median rPFS was 11.1 months. Among phase II patients (n = 144), 72.3% experienced grade 1\/2 treatment-related adverse events (TRAEs) and 17.4% experienced grade 3 TRAEs; no grade \u22654 TRAEs occurred. TRAEs led to dose reduction and discontinuation in 11.8% and 11.1% of patients, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Bavdegalutamide had a manageable safety profile and showed promising clinical activity in patients with mCRPC, particularly those with tumors harboring\n                      <jats:italic toggle=\"yes\">AR<\/jats:italic>\n                      T878\/H875 mutations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-02995","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:00:16Z","timestamp":1791576016000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Phase I\/II Study of Bavdegalutamide, a Proteolysis-Targeting Chimera Androgen Receptor Degrader, in Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.1200","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2346-068X","authenticated-orcid":true,"given":"Xin","family":"Gao","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2790-6235","authenticated-orcid":true,"given":"Benjamin","family":"Garmezy","sequence":"additional","affiliation":[{"name":"Sarah Cannon Research Institute, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5795-3361","authenticated-orcid":true,"given":"Jacqueline","family":"Vuky","sequence":"additional","affiliation":[{"name":"Oregon Health &amp; Science University, Portland, OR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6455-5553","authenticated-orcid":true,"given":"John","family":"Shen","sequence":"additional","affiliation":[{"name":"UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-7343","authenticated-orcid":true,"given":"Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Tulane University, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3938-2627","authenticated-orcid":true,"given":"Cora N.","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, NY"},{"name":"Meyer Cancer Center, New York Presbyterian Hospital, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0552-6912","authenticated-orcid":true,"given":"Robert","family":"Dreicer","sequence":"additional","affiliation":[{"name":"University of Virginia Comprehensive Cancer Center, Charlottesville, VA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0380-9465","authenticated-orcid":true,"given":"Maha","family":"Hussain","sequence":"additional","affiliation":[{"name":"Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3701-5084","authenticated-orcid":true,"given":"Arash","family":"Rezazadeh Kalebasty","sequence":"additional","affiliation":[{"name":"University of California Irvine Medical Center, Orange, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivor J.","family":"Percent","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists South, Port Charlotte, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1381-2713","authenticated-orcid":true,"given":"Elisabeth I.","family":"Heath","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Florida Cancer Specialists North, St Petersburg, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0010-8551","authenticated-orcid":false,"given":"Benjamin L.","family":"Maughan","sequence":"additional","affiliation":[{"name":"Huntsman Cancer Institute, University of Utah Comprehensive Cancer Center, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhi","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Landrette","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiachang","family":"Gong","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Healey","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janaki","family":"Parameswaran","sequence":"additional","affiliation":[{"name":"Arvinas Operations, Inc, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6165-5797","authenticated-orcid":true,"given":"Daniel P.","family":"Petrylak","sequence":"additional","affiliation":[{"name":"Smilow Cancer Center, Yale School of Medicine, New Haven, CT"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","published-online":{"date-parts":[[2026,10,9]]},"reference":[{"key":"e_1_3_9_2_2","first-page":"339","article-title":"Treatment landscape for patients with castration-resistant prostate cancer: Patient selection and unmet clinical needs","volume":"14","author":"Turco F","year":"2022","unstructured":"Turco F, Gillessen S, Cathomas R, et al: Treatment landscape for patients with castration-resistant prostate cancer: Patient selection and unmet clinical needs. 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