{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:20:42Z","timestamp":1792545642719,"version":"4.5.0"},"reference-count":31,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"15","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2025,5,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>FOR46, a fully human antibody conjugated to monomethyl auristatin E, targets a tumor-selective epitope of CD46, which is overexpressed in metastatic castration-resistant prostate cancer (mCRPC). FOR46 demonstrates potent nonclinical activity in enzalutamide-resistant CRPC models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      This was a phase I, first-in-human, dose escalation\/expansion study in patients with progressive mCRPC after treatment with \u2265one androgen signaling inhibitors (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03575819\">NCT03575819<\/jats:ext-link>\n                      ). The starting dose of FOR46 was 0.1 mg\/kg given intravenously every 3 weeks. The primary objective was to determine the maximally tolerated dose (MTD). Whole-blood mass cytometry (cytometry by time of flight) was used to characterize peripheral immune response and CD46 expression in CRPC tissue that underwent central pathology review.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Fifty-six patients were enrolled. Dose-limiting toxicities included neutropenia (n = 4), febrile neutropenia (n = 1), and fatigue (n = 1). The MTD was 2.7 mg\/kg using adjusted body weight. The most common grade \u22653 adverse events across all dose levels were neutropenia (59%), leukopenia (27%), lymphopenia (7%), anemia (7%), and fatigue (5%). One grade 3 febrile neutropenia event was observed. There were no treatment-related deaths. In the efficacy evaluable subset (patients with adenocarcinoma treated with a starting dose \u22651.2 mg\/kg, n = 40), the median radiographic progression-free survival was 8.7 months (range, 0.1-33.9). Fourteen of 39 evaluable patients (36%) achieved a PSA50 response. The confirmed objective response rate was 20% (5 of 25 RECIST-evaluable patients). The median duration of response was 7.5 months. Responders had a significantly higher on-treatment frequency of circulating effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>FOR46 demonstrated encouraging preliminary clinical activity with a manageable safety profile. Targeting CD46 elicited an immune priming effect that was associated with clinical outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-24-01989","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T16:04:03Z","timestamp":1743005043000},"page":"1824-1834","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":18,"title":["Phase I, First-in-Human Study of FOR46 (FG-3246), an Immune-Modulating Antibody-Drug Conjugate Targeting CD46, in Patients With Metastatic Castration-Resistant Prostate Cancer"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct03575819","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7003-7982","authenticated-orcid":true,"given":"Rahul R.","family":"Aggarwal","sequence":"first","affiliation":[{"name":"San Francisco Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA"}],"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\/0000-0003-4576-5034","authenticated-orcid":true,"given":"David","family":"VanderWeele","sequence":"additional","affiliation":[{"name":"Northwestern University Robert H. 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