ASCO 2019: Phase 1 Study of Pasotuxizumab, a PSMA-Targeting Bispecific T cell Engager Immunotherapy for Metastatic Castration-Resistant Prostate Cancer

Chicago, IL (UroToday.com) Bi-specific T-cell engagers (BiTEs) are a class of immunotherapeutic molecules which enhance a patient’s immune response by helping direct T cells to specific tumor cells.1 Pasotuxizumab is a BiTE which engages cells expressing prostate-specific membrane antigen (PSMA) and the CD3 epsilon subunit of the T cell receptor complex.2 In preclinical models, pasotuxizumab prevented growth of PC-3-huPSMA cells in NOD/SCID mice.3 Here, the authors present the results of the phase 1 study of pasotuxizumab for patients with metastatic castration-resistant prostate cancer (mCRPC).
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This abstract provides data on 16 patients enrolled in 5 dosing cohorts. All patients had metastatic castration-resistant prostate cancer (mCRPC) refractory to standard of care therapy as shown below.
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Anti-tumor activity was found to be dose dependent, with a mean prostate-specific antigen (PSA) change of -54.9% at a dose of 80 µg/d, compared with +0.74% at 5 µg/d. PSA50s were seen at the 20 µg/d, 40 µg/d, and 80 µg/d dose level, and two patients have durable PSA responses beyond one year (14 months and 19 months).
ASCO2019_poster146_table3.pngASCO2019_poster146_changeinPSA.png
In terms of safety, the most common adverse events (AEs) were fever (94%), chills (69%), and fatigue (50%). 81% of patients had a grade 3 adverse event – most common grade 3 AEs were decreased lymphocytes and infections, both at 44%. The full serious adverse events (SAE) list below is similar to what is seen in BITE therapies in lymphoma.
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Pasotuxizumab is a prostate-specific membrane antigen (PSMA) targeting BiTE which was shown to be active against mCRPC in this study, with several patients experiencing a PSA50 and two patients with durable responses over one year. The side effect profile mimics the same symptoms as cytokine release syndrome which has been seen with other BiTEs used in hematologic malignancies, notably fever and chills which were experienced by the majority of patients. This study demonstrates that BiTEs may be another effective way to deliver an immunotherapy option for patients with mCRPC.

Presented by: Horst-Dieter Hummel, MD, University Hospital of Wuerzburg, Germany

Written by: Jason Zhu, MD. Fellow, Division of Hematology and Oncology, Duke University, @TheRealJasonZhu at the 2019 ASCO Annual Meeting #ASCO19, May 31- June 4, 2019, Chicago, IL USA

References:
  1. Huehls AM, Coupet TA, Sentman CL. Bispecific T‐cell engagers for cancer immunotherapy. Immunology and cell biology 2015;93:290-6.
  2. Lutterbuese R, Friedrich M, Kischel R, et al. Preclinical characterization of MT112/BAY 2010112, a novel PSMA/CD3-bispecific BiTE antibody for the treatment of prostate cancer. AACR; Cancer Res 2011;71(8 Suppl): Abstract nr 4561.
  3. Friedrich M, Raum T, Lutterbuese R, et al. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-Bispecific BiTE antibody cross-reactive with non-human primate antigens. Molecular cancer therapeutics 2012;11:2664-73.
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