Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).

Publication ,  Conference
Kelly, WK; Pook, DW; Appleman, LJ; Waterhouse, DM; Horvath, L; Edenfield, WJ; Matsubara, N; Danila, DC; Aggarwal, RR; Petrylak, DP; Sartor, AO ...
Published in: Journal of Clinical Oncology
February 20, 2021

TPS183 Background: Six transmembrane epithelial antigen of the prostate 1 (STEAP1) is a cell surface antigen that is highly expressed in prostate cancer. AMG 509 is a potent bispecific XmAb 2+1 immune therapy designed to direct T effector cells to STEAP1-expressing cells. AMG 509 contains two identical humanized anti-STEAP1 Fab domains that bind STEAP1-expressing cells, an anti-CD3 scFv domain that binds T cells, and an Fc domain, engineered to lack effector function, that extends serum half-life. In preclinical studies, AMG 509 induced potent and specific T-cell-mediated lysis of STEAP1-expressing cancer models. Methods: This open-label, phase 1, first-in-human study will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of AMG 509 in patients with relapsed/refractory mCRPC. The dose exploration phase (n=40) will estimate the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) using a Bayesian logistic regression model. The dose expansion phase (n=30) will confirm safety, PK, and pharmacodynamics at the MTD or RP2D and collect further safety, efficacy, and biomarker data. Efficacy will be assessed by prostate-specific antigen response, circulating tumor cell response, and objective tumor response per RECIST 1.1 with Prostate Cancer Working Group 3 modifications. Key inclusion criteria: men ≥18 years with histologically/cytologically confirmed mCRPC who are refractory to novel hormonal therapy (e.g., abiraterone and/or enzalutamide) and have failed 1–2 taxane regimens or are medically unsuitable for or have refused taxanes; ongoing castration with total serum testosterone ≤50 ng/dL; evidence of progressive disease; ECOG performance status 0–1; life expectancy ≥3 months; and adequate hematologic, renal, hepatic, and cardiac function. In the dose exploration phase, novel antiandrogen therapy must have been given in the metastatic setting. Key exclusion criteria: pure small cell or neuroendocrine carcinoma of the prostate; untreated CNS metastases or leptomeningeal disease; any anticancer therapy or immunotherapy, radiation therapy, or major surgery <4 weeks from first dose; history of or current autoimmune disease or any disease requiring immunosuppressive therapy (≤10 mg/d prednisone permitted); prior STEAP1-targeted therapy; infection requiring IV antimicrobials <7 days from first dose. The study opened in January 2020 and is recruiting patients. ClinicalTrials.gov: NCT04221542. 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved. Clinical trial information: NCT04221542.

Duke Scholars

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

TPS183 / TPS183

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kelly, W. K., Pook, D. W., Appleman, L. J., Waterhouse, D. M., Horvath, L., Edenfield, W. J., … Dorff, T. B. (2021). Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). In Journal of Clinical Oncology (Vol. 39, pp. TPS183–TPS183). American Society of Clinical Oncology (ASCO). https://doi.org/10.1200/jco.2021.39.6_suppl.tps183
Kelly, William Kevin, David William Pook, Leonard Joseph Appleman, David Michael Waterhouse, Lisa Horvath, William Jeffery Edenfield, Nobuaki Matsubara, et al. “Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).” In Journal of Clinical Oncology, 39:TPS183–TPS183. American Society of Clinical Oncology (ASCO), 2021. https://doi.org/10.1200/jco.2021.39.6_suppl.tps183.
Kelly WK, Pook DW, Appleman LJ, Waterhouse DM, Horvath L, Edenfield WJ, et al. Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). In: Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS183–TPS183.
Kelly, William Kevin, et al. “Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC).Journal of Clinical Oncology, vol. 39, no. 6_suppl, American Society of Clinical Oncology (ASCO), 2021, pp. TPS183–TPS183. Crossref, doi:10.1200/jco.2021.39.6_suppl.tps183.
Kelly WK, Pook DW, Appleman LJ, Waterhouse DM, Horvath L, Edenfield WJ, Matsubara N, Danila DC, Aggarwal RR, Petrylak DP, Sartor AO, Sumey CJ, Adra N, Armstrong AJ, Cheng F-C, Stieglmaier J, Kouros-Mehr H, Dorff TB. Phase I study of AMG 509, a STEAP1 x CD3 T-cell recruiting XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC). Journal of Clinical Oncology. American Society of Clinical Oncology (ASCO); 2021. p. TPS183–TPS183.

Published In

Journal of Clinical Oncology

DOI

EISSN

1527-7755

ISSN

0732-183X

Publication Date

February 20, 2021

Volume

39

Issue

6_suppl

Start / End Page

TPS183 / TPS183

Publisher

American Society of Clinical Oncology (ASCO)

Related Subject Headings

  • Oncology & Carcinogenesis
  • 3211 Oncology and carcinogenesis
  • 1112 Oncology and Carcinogenesis
  • 1103 Clinical Sciences