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340 Phase 1 study of AMG 160, a half-life extended BiTE® (bispecific T-cell engager) therapy targeting prostate-specific membrane antigen, in patients with metastatic castration-resistant prostate cancer
  1. Tanya Dorff1,
  2. Matthew Rettig2,
  3. Jean-Pascal Machiels3,
  4. Martijn Lolkema4,
  5. Karen Autio4,
  6. Richard Greil6,
  7. Sylvie Rottey7,
  8. Nabil Adra8,
  9. Mark Salvati9,
  10. Shirley Poon9,
  11. Daniel Tan10,
  12. Gabor Jurida9,
  13. Hosein Kouros-Mehr9,
  14. Karim Fizazi11,
  15. Ben Tran12 and
  16. Lisa Horvath13
  1. 1City of Hope, Duarte, CA, United States
  2. 2UCLA, Los Angeles, CA, United States
  3. 3Cliniques Universitaires Saint-Luc, Brussels, Belgium
  4. 4Erasmus MC Cancer Institute, Rotterdam, Netherlands
  5. 5Memorial Sloan Kettering Cancer Center, New York, NY, United States
  6. 6IIIrd Medical Department, Paracelsus Me, Salzburg, Austria
  7. 7Drug Research Unit Ghent, Ghent, Belgium
  8. 8Indiana University School of Medicine, Indianapolis, IN, United States
  9. 9Amgen Inc, Thousand Oaks, CA, United States
  10. 10National Cancer Centre Singapore, Singapore, Singapore
  11. 11University of Paris Sud, Villejuif, France
  12. 12Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
  13. 13Chris O’Brien Lifehouse, Camperdown, Australia


Background Prostate-specific membrane antigen (PSMA) is a clinically validated target for metastatic castration-resistant prostate cancer (mCRPC). AMG 160 BiTE® immuno-oncology therapy redirects T cells to cancer cells by binding to PSMA on cancer cells and CD3 on T cells, leading to T-cell activation, tumor-cell killing, and T-cell expansion. As the BiTE mode of action leads to an upregulation of immune checkpoints, combining AMG 160 with a PD-1 inhibitor may lead to sustained T cell–dependent killing of tumor cells. Cytokine release syndrome (CRS) is a first-dose effect induced by BiTE molecule-mediated T-cell activation. An approach to mitigate CRS is prophylaxis with an anti-inflammatory agent.

Methods The phase 1 study (NCT03792841) has four parts: AMG 160 monotherapy; AMG 160 in combination with pembrolizumab; AMG 160 monotherapy with etanercept prophylaxis; and AMG 160 monotherapy administered in outpatient centers with 24-hour monitoring. Included in the study are men with histologically/cytologically confirmed mCRPC who are refractory to novel androgen receptor signaling inhibitors: abiraterone, enzalutamide, darolutamide, and/or apalutamide and have failed, refused, or are unsuitable for taxanes; and who have ongoing castration with evidence of progressive disease. Patients who received prior PSMA radionuclide therapy are eligible. Patients with CNS metastases, leptomeningeal disease, spinal cord compression, or active autoimmune disease are excluded. Primary objectives are to evaluate safety and tolerability and determine the MTD or RP2D of AMG 160 monotherapy or in combination with pembrolizumab. Secondary objectives are to characterize pharmacokinetics and preliminary antitumor activity. Evaluation of preliminary antitumor activity will be based on RECIST 1.1 with Prostate Cancer Working Group 3 modifications, PSA response, CTC response, progression-free survival (radiographic and PSA), and overall survival. PSMA PET/CT and FDG PET/CT imaging will be used for evaluation of exploratory objectives (figure 1). The study opened in February 2019 and is currently recruiting patients.

Abstract 340 Figure 1

Study schema

Results N/A

Conclusions N/A

Trial Registration NCT03792841

Ethics Approval The study was approved by all institutional ethics boards.

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