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717 AMG 160, a prostate-specific membrane antigen (PSMA)-targeted BiTE® immuno-oncology therapy, is active in models of advanced prostate cancer that are resistant to radioligand therapy
  1. Katharina Lueckerath1,
  2. Julie Bailis2,
  3. Kyle Current1,
  4. Mark Salvati2,
  5. Caius Radu1 and
  6. Johannes Czernin1
  1. 1David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
  2. 2Amgen Inc., San Francisco, CA, USA


Background AMG 160 is an HLE BiTE® (half-life extended bispecific T-cell engager) that binds PSMA on prostate cancer cells and CD3 on T-cells and induces redirected T-cell lysis of PSMA-expressing cells. This mechanism may allow the BiTE molecule to be active in settings where other targeted or immune therapies have failed. Here, we evaluated the activity of AMG 160 in mouse models of advanced prostate cancer that are resistant to 177Lu-PSMA-617, a PSMA-targeted radioligand therapy that has emerged as a promising treatment modality for metastatic castration-resistant prostate cancer (mCRPC).

Methods Two prostate cancer models were tested in 6–8-week-old male NCG mice: one cohort had established subcutaneous C4-2 TP53-/- tumors (C4-2 cells with TP53 knockout), and the other cohort had established systemic C4-2 TP53wt/wttumors that mimic metastatic lesions (intracardiac injection). PSMA levels in both models (~255,000 PSMA/cell) are sufficient for tumor growth inhibition with 177Lu-PSMA-617. Mice were administered a single intravenous (IV) infusion of human T-cells. Three days later, mice were treated with 1 cycle of 177Lu-PSMA-617 (30 MBq, IV), or 3 weekly doses of AMG 160 (1 mg/kg, IV) or of a control HLE BiTE molecule (1 mg/kg, IV; target not expressed on C4-2 cells). Therapeutic efficacy was assessed by tumor burden measurements, time to progression (TTP), and survival.

Results In both prostate cancer models, AMG 160 treatment significantly improved disease control (figure 1). Median TTP was not reached in the AMG 160 group (p<0.0001), whereas it was 31d (177Lu-PSMA-617) and 23.5d (control) in the subcutaneous model, and 68d (177Lu-PSMA-617) and 50.5d (control) in the systemic model. Median survival was not reached in the AMG 160 group (p<0.0001); it was 39d (177Lu-PSMA-617) and 26.5d (control) in the subcutaneous model, and 77d (177Lu-PSMA-617) and 61d (control) in the systemic model. Following treatment with AMG 160, 2/10 mice with subcutaneous and 7/9 mice with systemic tumors had not progressed at the end of the observation period (>100 days). In contrast, all mice in the 177Lu-PSMA-617 and control groups succumbed to progressive disease.

Abstract 717 Figure 1

AMG 160 treatment extended survival in mouse models of advanced prostate cancer

Conclusions Our study demonstrates potent antitumor activity of AMG 160 monotherapy in models of metastatic CRPC that are resistant to PSMA-targeted radioligand therapy with 177Lu-PSMA-617. These data provide a rationale for evaluating AMG 160 in patients with mCRPC who have progressed on 177Lu-PSMA-617. AMG 160 is currently being evaluated in a phase 1 study in patients with mCRPC (NCT03792841).

Acknowledgements The authors would like to acknowledge Micah Robinson, PhD of Amgen Inc. for medical writing support and Hosein Kouros-Mehr, MD, PhD of Amgen Inc. for facilitating the collaboration and helpful discussions.

Trial Registration ClinicalTrials. gov Identifier: NCT03792841

Ethics Approval All animal experimental protocols were approved by the UCLA Animal Research Committee (# 2005-090).

This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:

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