{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T18:16:17Z","timestamp":1790100977061,"version":"4.0.1"},"reference-count":36,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"unspecified","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2020,8,24]]},"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Prostate cancer is the second most common cancer in men worldwide. When the disease becomes resistant to androgen-deprivation therapy, treatment options are sparse. To address the high medical need in castration-resistant prostate cancer (CRPC), we generated a novel PSMAxCD3 bispecific antibody termed CC-1. CC-1 binds to prostate-specific membrane antigen that is expressed on prostate cancer cells and tumour vessels, thereby allowing a dual anticancer effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>\n                      This first in human clinical study is a prospective and multicentre trial which enrols patients with metastatic CRPC after failure of established third-line therapy. CC-1 is applied after prophylactic interleukin-6 receptor blockade with tocilizumab (once 8\u2009mg\/kg body weight). Each patient receives at least one cycle of CC-1 over a time course of 7 days in an inpatient setting. If clinical benefit is observed, up to five additional cycles of CC-1 can be applied. The study is divided in two parts: (1) a dose escalation phase with intraindividual dose increase from 28\u2009\u00b5g to the target dose of 1156\u2009\u00b5g based on a modified fast titration design by Simon\n                      <jats:italic>et al<\/jats:italic>\n                      to determine safety, tolerability and the maximum tolerated dose (MTD) as primary endpoints and (2) a dose expansion phase with additional 14 patients on the MTD level of part (1) to identify first signs of efficacy. Secondary endpoints compromise overall safety, tumour response, survival and a translational research programme with, among others, the analysis of CC-1 half-life, the induced immune response, as well as the molecular profiling in liquid biopsies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The PSMAxCD3 study was approved by the Ethics Committee of The University Hospital T\u00fcbingen (100\/2019AMG1) and the Paul-Ehrlich-Institut (3684\/02). Clinical trial results will be published in peer-reviewed journals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration numbers<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov Registry (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT04104607\">NCT04104607<\/jats:ext-link>\n                      ) and ClinicalTrials.eu Registry (EudraCT2019-000238-20).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-039639","type":"journal-article","created":{"date-parts":[[2020,10,16]],"date-time":"2020-10-16T17:50:04Z","timestamp":1602870604000},"page":"e039639","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Protocol of a prospective, multicentre phase I study to evaluate the safety, tolerability and preliminary efficacy of the bispecific PSMAxCD3 antibody CC-1 in patients with castration-resistant prostate carcinoma"],"prefix":"10.1136","volume":"10","clinical-trial-number":[{"clinical-trial-number":"nct04104607","registry":"10.18810\/clinical-trials-gov","type":"preResults"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7305-8620","authenticated-orcid":false,"given":"Jonas S","family":"Heitmann","sequence":"first","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliane S","family":"Walz","sequence":"additional","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Pfl\u00fcgler","sequence":"additional","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kauer","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard F","family":"Schlenk","sequence":"additional","affiliation":[{"name":"National Center of Tumor Diseases-Trial Center, National Center of Tumor Diseases, German Cancer Research Center, Heidelberg, Germany"},{"name":"Department of Internal Medicine VI, Heidelberg University Hospital, Heidelberg, Germany"},{"name":"Department of Internal Medicine V, Heidelberg University Hospital, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gundram","family":"Jung","sequence":"additional","affiliation":[{"name":"Institute for Cell Biology, Department of Immunology, University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut R","family":"Salih","sequence":"additional","affiliation":[{"name":"Clinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital T\u00fcbingen, T\u00fcbingen, Germany"},{"name":"Cluster of Excellence iFIT (EXC2180) 'Image-Guided and Functionally Instructed Tumor Therapies', University of T\u00fcbingen, T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2020,10,16]]},"reference":[{"key":"2025120521292889000_10.10.e039639.1","unstructured":"WHO . 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