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
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...
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| Main Authors: | , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
October 16, 2020
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| In: |
BMJ open
Year: 2020, Volume: 10, Issue: 10, Pages: 1-9 |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2020-039639 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1136/bmjopen-2020-039639 Verlag, lizenzpflichtig, Volltext: https://bmjopen.bmj.com/content/10/10/e039639 
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| Author Notes: | Jonas S. Heitmann, Juliane S. Walz, Martin Pflügler, Joseph Kauer, Richard F. Schlenk, Gundram Jung, Helmut R. Salih |
| Summary: | 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). |
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| Item Description: | Gesehen am 10.05.2021 |
| Physical Description: | Online Resource |
| ISSN: | 2044-6055 |
| DOI: | 10.1136/bmjopen-2020-039639 |