{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:59:00Z","timestamp":1789545540201,"version":"build-2803163510"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"9","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIA BC 010547"],"award-info":[{"award-number":["ZIA BC 010547"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the clinical efficacy of enzalutamide monotherapy in patients with advanced prostate cancer, therapeutic resistance and disease progression are inevitable. We proposed a study to evaluate NLG207, a nanoparticle-drug conjugate (NDC) of the potent topoisomerase I inhibitor camptothecin, in combination with enzalutamide, in patients with metastatic castration-resistant prostate cancer (mCRPC) following progression on enzalutamide.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a single-arm, optimal two-stage, phase II study to evaluate the efficacy of NLG207 in combination with enzalutamide in patients with mCRPC who received prior enzalutamide. A lead-in dose escalation evaluated the recommended phase 2 dose of NLG207 in combination with enzalutamide. Patients received NLG207 via IV infusion every 2 weeks and enzalutamide 160 mg orally once daily.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between March 2019 and June 2021, four patients were accrued to the lead-in dose escalation. Two of the four patients were evaluable and both experienced DLTs at the NLG207 12 mg\/m2 dose level; one DLT was related to a dose delay for noninfective cystitis and myelosuppression, the other a grade 3 noninfective cystitis. Further evaluation of NLG207 in combination with enzalutamide was halted and the study was ultimately terminated. PSA declines from baseline were observed in two patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NLG207 12 mg\/m2 in combination with enzalutamide was not well tolerated in patients with mCRPC following several lines of the standard of care therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>ClinicalTrials.gov Identifier<\/jats:title><jats:p>NCT03531827.<\/jats:p><\/jats:sec>","DOI":"10.1093\/oncolo\/oyac100","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T03:20:53Z","timestamp":1650943253000},"page":"718-e694","source":"Crossref","is-referenced-by-count":25,"title":["A Single-arm Phase II Study Combining NLG207, a Nanoparticle Camptothecin, with Enzalutamide in Advanced Metastatic Castration-resistant Prostate Cancer Post-Enzalutamide"],"prefix":"10.1093","volume":"27","author":[{"given":"Keith T","family":"Schmidt","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatima","family":"Karzai","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijo","family":"Bilusic","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa M","family":"Cordes","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy H","family":"Chau","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody J","family":"Peer","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Wroblewski","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alwin D R","family":"Huitema","sequence":"additional","affiliation":[{"name":"Department Pharmacy & Pharmacology, Netherlands Cancer Institute , Amsterdam , The Netherlands"},{"name":"Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht University , Utrecht , The Netherlands"},{"name":"Department of Pharmacology, Princess M\u00e1xima Center for Pediatric Oncology , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H M","family":"Schellens","sequence":"additional","affiliation":[{"name":"Utrecht Institute of Pharmaceutical Sciences, Utrecht University , Utrecht , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6569-2912","authenticated-orcid":false,"given":"James L","family":"Gulley","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L","family":"Dahut","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2428-5613","authenticated-orcid":false,"given":"William D","family":"Figg","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"},{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-8636","authenticated-orcid":false,"given":"Ravi A","family":"Madan","sequence":"additional","affiliation":[{"name":"Genitourinary Malignancies Branch, Center for Cancer Research, 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