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

• Verfasst von: Heitmann, Jonas S. [VerfasserIn]
• Verfasst von: Walz, Juliane S. [VerfasserIn]
• Verfasst von: Pflügler, Martin [VerfasserIn]
• Verfasst von: Kauer, Joseph [VerfasserIn]
• Verfasst von: Schlenk, Richard Friedrich [VerfasserIn]
• Verfasst von: Jung, Gundram [VerfasserIn]
• Verfasst von: Salih, Helmut R. [VerfasserIn]
• Titel: 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
• Verf.angabe: Jonas S. Heitmann, Juliane S. Walz, Martin Pflügler, Joseph Kauer, Richard F. Schlenk, Gundram Jung, Helmut R. Salih
• E-Jahr: 2020
• Jahr: October 16, 2020
• Umfang: 9 S.
• Teil: volume:10
• Teil: year:2020
• Teil: number:10
• Teil: elocationid:e039639
• Teil: pages:1-9
• Teil: extent:9
• Fussnoten: Gesehen am 10.05.2021
• Titel Quelle: Enthalten in: BMJ open
• Ort Quelle: London : BMJ Publishing Group, 2011
• Jahr Quelle: 2020
• Band/Heft Quelle: 10(2020), 10, Artikel-ID e039639, Seite 1-9
• ISSN Quelle: 2044-6055
• DOI: doi:10.1136/bmjopen-2020-039639
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: adult oncology
• Sach-SW: immunology
• Sach-SW: urological tumours
• K10plus-PPN: 1757541012

Abstract

Introduction 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. - Methods and analysis 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 et al 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. - Ethics and dissemination 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. - Trial registration numbers ClinicalTrials.gov Registry (NCT04104607) and ClinicalTrials.eu Registry (EudraCT2019-000238-20).