ASCO 2021: Phase I Study of CCW702, A Bispecific Small Molecule-Antibody Conjugate Targeting PSMA and CD3 in Patients with mCRPC

(UroToday.com) CCW702 is a novel bispecific antibody comprised of a small molecule imaging agent ligand (DUPA) with specificity for prostate-specific membrane antigen (PSMA) conjugated to an anti-CD3 antibody via an unnatural amino acid. This format has the structure of an antibody drug conjugate with the activity of a CD3-engaging bispecific antibody.



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Preclinical data suggest efficacy in the xenograft model, with near complete bioavailability when administered subcutaneously at 66 ug/kg. The design of CCW702 was leveraged to optimize the structure and function of T cell redirected cytotoxicity against PSMA-positive prostate cancer tumors in preclinical development. At the 2021 ASCO virtual annual program, Dr. Mark Markowski and colleagues discussed the design of this phase I trial.

This is a first-in-human, open-label, multi-center phase 1 study evaluating the safety and tolerability of CCW702 when administered via subcutaneous injection in men with mCRPC. This study will be conducted in two parts:

  • Part I, a dose escalation to determine the maximum tolerated dose and recommended phase 2 dose
  • Part II, a dose expansion to determine efficacy at the recommended phase 2 dose

The trial schema is as follows:

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Safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy will be evaluated. Efficacy will be assessed by change in circulating tumor cells, PSA50 response rate, and objective tumor response by RECIST v1.1. Key biomarkers include characterization of circulating tumor cells, T cell phenotyping in peripheral blood, chemokines and cytokines over time, and evaluation of available tumor biopsies by immunohistochemistry.

Key inclusion criteria include men age ≥ 18 years with histologically or cytologically confirmed adenocarcinoma who, in the metastatic setting, have progressed on at least one novel androgen receptor-targeted therapy. Up to one prior chemotherapy regimen is allowed.  Key exclusion criteria include patients with primarily neuroendocrine differentiation or small cell features on histopathology, patients with a history of grade >= 3 immune-related adverse events or any grade immune related adverse events that required immune suppression, and patients with new or progressive brain metastasis or leptomeningeal disease.

This study will enroll 20-30 patients in Part 1 and approximately 40 patients in Part 2. The study opened in December 2019 and is currently enrolling in the dose escalation phase at the following site: Johns Hopkins University, Karmanos Cancer Institute (Detroit, MI), Medical College of Wisconsin, University of California San Diego, and University of Virginia.

Clinical trial information: NCT04077021

Presented by: Mark C. Markowski, MD, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore

Co-Authors: Deepak Kilari, Mario A. Eisenberger, Rana R. McKay, Robert Dreicer, Mohit Trikha, Elisabeth I. Heath, Jing Li, Pamela D. Garzone, Travis S. Young; The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD; Medical College of Wisconsin, Milwaukee, WI; University of California San Diego, Moores Cancer Center, La Jolla, CA; University of Virginia, Charlottesville, VA; Triphase Accelerator, San Diego, CA; Karmanos Cancer Institute, Department of Oncology, Wayne State University School of Medicine, Detroit, MI; Calibr, a division of Scripps Research, La Jolla, CA; Rinat-Pfizer, South San Francisco, CA; Calibr, San Diego, CA