The Bispecific PSMAxCD3 Antibody CC-1 in Patients with Castration Resistant Prostate Carcinoma

Summary

This trial is a first in human (FIH) study in patients with castration resistant metastatic prostate cancer (CRPC) after failure of third-line therapy aiming to evaluate safety and efficacy of CC-1, a bispecific antibody (bsAb) with PSMAxCD3 specificity developed within DKTK. CC-1 binds to human prostate-specific membrane antigen (PSMA) on prostate cancer cells as well as to tumor vessels of CRPC, thereby allowing for a dual mode of anti-cancer action. CC-1 was developed in a novel format which not only prolongs serum half-life but most importantly reduces off-target T cell activation with expected fewer side effects. Together with preemptive IL-6 receptor (IL-6R) blockade using tocilizumab, this allows for application of effective bsAb doses with expected high anticancer activity. The study comprises two phases. The first phase is a doseescalation phase with concomitant prophylactic application of tocilizumab to evaluate the maximally tolerated dose (MTD) of CC-1. This is followed by a dose-expansion phase (also with prophylactic IL-6R blockade using tocilizumab), as this approach has been shown to be efficient and beneficial for patients. A translational research program comprising, among others, analysis of CC-1 half-life and the induced immune response as well as molecular profiling in liquid biopsies will serve to better define the mode of action of CC-1 and to identify biomarkers for further clinical development.

Timeline

Start

2019-11-15

Primary completion

2025-12-31

Completion

2025-12-31

Publications

• Lutz MS, Klimovich B, Maurer S, Heitmann JS, Marklin M, Zekri L, Jung G, Salih HR, Hinterleitner C. Platelets subvert antitumor efficacy of T cell-recruiting bispecific antibodies. J Immunother Cancer. 2022 Feb;10(2):e003655. doi: 10.1136/jitc-2021-003655.
• Heitmann JS, Walz JS, Pflugler M, Kauer J, Schlenk RF, Jung G, Salih HR. 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. BMJ Open. 2020 Oct 16;10(10):e039639. doi: 10.1136/bmjopen-2020-039639.

Drugs

Indications