{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(10)"],"submitter":["Heitmann JS"],"pubmed_abstract":["<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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 mg/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 µg to the target dose of 1156 µg based on a modified fast titration design by Simon <i>et al</i> 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.<h4>Ethics and dissemination</h4>The PSMAxCD3 study was approved by the Ethics Committee of The University Hospital Tübingen (100/2019AMG1) and the Paul-Ehrlich-Institut (3684/02). Clinical trial results will be published in peer-reviewed journals.<h4>Trial registration numbers</h4>ClinicalTrials.gov Registry (NCT04104607) and ClinicalTrials.eu Registry (EudraCT2019-000238-20)."],"journal":["BMJ open"],"pagination":["e039639"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7569941"],"repository":["biostudies-literature"],"pubmed_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."],"pmcid":["PMC7569941"],"pubmed_authors":["Jung G","Pflugler M","Schlenk RF","Salih HR","Heitmann JS","Walz JS","Kauer J"],"additional_accession":[]},"is_claimable":false,"name":"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.","description":"<h4>Introduction</h4>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.<h4>Methods and analysis</h4>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 mg/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 µg to the target dose of 1156 µg based on a modified fast titration design by Simon <i>et al</i> 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.<h4>Ethics and dissemination</h4>The PSMAxCD3 study was approved by the Ethics Committee of The University Hospital Tübingen (100/2019AMG1) and the Paul-Ehrlich-Institut (3684/02). Clinical trial results will be published in peer-reviewed journals.<h4>Trial registration numbers</h4>ClinicalTrials.gov Registry (NCT04104607) and ClinicalTrials.eu Registry (EudraCT2019-000238-20).","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Oct","modification":"2026-05-05T01:14:12.6Z","creation":"2020-10-29T12:35:00Z"},"accession":"S-EPMC7569941","cross_references":{"pubmed":["33067297"],"doi":["10.1136/bmjopen-2020-039639"]}}