3535 - A phase 1 study of AMG 160, a half-life extended bispecific T cell engager (HLE BiTE) immuno-oncology therapy targeting PSMA, in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)

Background

Prostate specific membrane antigen (PSMA) is a clinically validated target for the imaging of prostate cancer, and studies with therapeutic PSMA-targeted radionuclides are ongoing. A recent trial with pasotuxizumab (AMG 212), a canonical BiTE^® molecule targeting PSMA, demonstrated preliminary antitumor activity in mCRPC. AMG 160 is a novel HLE BiTE^® immuno-oncology therapy that directs T effector cells to tumor cells via dual binding to CD3 and PSMA.

Trial design

This open-label, ascending, multiple dose, phase 1 study (NCT03792841) will evaluate safety and tolerability, determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), characterize pharmacokinetics, and evaluate preliminary efficacy of AMG 160 in pts with mCRPC. The dose exploration will estimate the MTD or RP2D via Bayesian logistic regression modeling. The dose expansion will confirm the safety and tolerability of the selected dose and further evaluate pharmacodynamics and antitumor activity. AMG 160 will be given as a short-term IV infusion. In cycle 1, dexamethasone will be given within 1 hour prior to each dose of AMG 160; pts will be hospitalized for ≥72 hours after each AMG 160 infusion in cycle 1. Key inclusion criteria: age ≥18 years; histologically or cytologically confirmed mCRPC refractory to enzalutamide, abiraterone, and/or apalutamide; have failed 1–2 taxane-based regimens or are medically unsuitable for or refuse a taxane regimen; bilateral orchiectomy or on continuous androgen-deprivation therapy; evidence of progressive disease. Key exclusion criteria: active autoimmune disease or any other disease requiring immunosuppressive therapy (low dose prednisone permitted); central nervous system metastases or leptomeningeal disease; prior PSMA-targeted therapy. Preliminary antitumor activity will be assessed by RECIST 1.1 criteria with PCWG3 modifications, PSA response, duration of response, response as evaluated by ⁶⁸Ga-PSMA-11 PET/CT and ¹⁸F-FDG PET/CT imaging, PFS/OS, and circulating tumor cell endpoints (CTC0 and CTC conversion). The study opened in January 2019; dose exploration is ongoing.

Clinical trial identification

NCT03792841.

Editorial acknowledgement

Dianne Tomita, MPH, a consultant to Amgen Inc.

Legal entity responsible for the study

Amgen Inc.

Funding

Amgen Inc.

Disclosure

B. Tran: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Research grant / Funding (institution), Non-remunerated activity/ies: Janssen-Cilag; Advisory / Consultancy, Research grant / Funding (institution): MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Tolmar; Advisory / Consultancy, Research grant / Funding (self): Ipsen; Research grant / Funding (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (self): Pfizer; Research grant / Funding (self), Research grant / Funding (institution): Servier; Research grant / Funding (institution): Aslan; Research grant / Funding (institution): GSK; Research grant / Funding (institution): Taiho; Research grant / Funding (institution): Akeso; Research grant / Funding (institution): Aptevo; Leadership role: ANZUP; Leadership role: GU Tumor Group - Cancer Trials Australia; Leadership role: Molecular Tumour Board - Victorian Comprehensive Cancer Centre. H. Kouros-Mehr: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. A. Fermin: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen. L. Horvath: Research grant / Funding (self), Travel / Accommodation / Expenses: Astellas; Shareholder / Stockholder / Stock options, Spouse / Financial dependant, Spouse is an executive at this company: Connected Medical Solutions Pty Ltd. M. Rettig: Research grant / Funding (self): Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Johnson & Johnson. T. Dorff: Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Roche; Advisory / Consultancy: Seattle Genetics; Speaker Bureau / Expert testimony: Exelixis. S.T. Tagawa: Advisory / Consultancy, Research grant / Funding (institution): Medivation; Advisory / Consultancy, Research grant / Funding (institution): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Endocyte; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Immunomedics; Advisory / Consultancy, Research grant / Funding (institution): Karyopharm Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): AbbVie; Advisory / Consultancy: Tolmar; Advisory / Consultancy: QED; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Sanofi; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Progenics; Research grant / Funding (institution): Millenium; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Rexahn Pharmaceuticals; Research grant / Funding (institution): Newlink Genetics; Research grant / Funding (institution): Inovio Pharmaceuticals; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): AVEO; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Stem CentRx; Research grant / Funding (institution): Exelixis; Research grant / Funding (institution): Clovis. S.K. Subudhi: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Janssen; Research grant / Funding (self): Bristol-Myers Squibb; Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Valeant; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Dendreon; Honoraria (self), Advisory / Consultancy, Shareholder / Stockholder / Stock options: Apricity Health; Honoraria (self), Advisory / Consultancy: Polaris; Advisory / Consultancy, Travel / Accommodation / Expenses: Amgen; Speaker Bureau / Expert testimony: Bayer Healthcare Pharmaceuticals; Honoraria (self), Travel / Accommodation / Expenses: Compugen; Honoraria (self), Travel / Accommodation / Expenses: Parker Institute of Cancer Immunology. E.S. Antonarakis: Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Janssen; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Dendreon; Honoraria (self), Advisory / Consultancy: Medivation; Honoraria (self), Advisory / Consultancy: ESSA; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Clovis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (self): Merck; Research grant / Funding (self): Johnson & Johnson; Research grant / Funding (self): Genentech; Research grant / Funding (self): Novartis; Research grant / Funding (self): Bristol-Myers Squibb; Honoraria (institution), Advisory / Consultancy: Eli Lilly; Licensing / Royalties: Qiagen. A.J. Armstrong: Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Dendreon; Research grant / Funding (institution): Novartis; Advisory / Consultancy: Sanofi Aventis; Research grant / Funding (institution): Genentech/Roche; Research grant / Funding (institution): Constellation; Advisory / Consultancy, Research grant / Funding (institution): Merck; Research grant / Funding (institution): BMS; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (self): ADA Cap; Advisory / Consultancy: Amgen; Advisory / Consultancy, Research grant / Funding (self): Astellas; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Bayer; Shareholder / Stockholder / Stock options: Bellicum; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (self): Bristol Myer Squibb; Advisory / Consultancy, Research grant / Funding (self): Clovis; Advisory / Consultancy, Research grant / Funding (self): Eli Lilly; Research grant / Funding (self): Endocyte; Advisory / Consultancy: Exelixis; Research grant / Funding (self): Genentech; Advisory / Consultancy: Incyte; Research grant / Funding (self): Innocrin; Advisory / Consultancy: Janssen; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Pharmacyclics; Research grant / Funding (self): Progenics; Advisory / Consultancy, Research grant / Funding (self): Roche Laboratories; Research grant / Funding (self): Sanofi Aventis; Advisory / Consultancy, Research grant / Funding (self): Seattle Genetics; Shareholder / Stockholder / Stock options: Tyme; Advisory / Consultancy: Urogen. K. Fizazi: Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: AAA; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Clovis; Honoraria (self), Advisory / Consultancy: CureVac; Honoraria (self), Advisory / Consultancy: Incyte; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Orion; Honoraria (self), Advisory / Consultancy: Sanofi. M.E. Salvati: Shareholder / Stockholder / Stock options, Full / Part-time employment: Amgen; Full / Part-time employment: Kite; Shareholder / Stockholder / Stock options: BMS. H.I. Scher: Travel / Accommodation / Expenses, Shareholder / Stockholder / Stock options, Officer / Board of Directors: Asterias Biotherapeutics; Advisory / Consultancy, Travel / Accommodation / Expenses: Ambry Genetics Corporation/Konica Minolta; Non-remunerated activity/ies: Janssen Biotech Inc; Non-remunerated activity/ies: Janssen Research & Development; Travel / Accommodation / Expenses, Non-remunerated activity/ies: ESSA Pharma Inc; Travel / Accommodation / Expenses, Non-remunerated activity/ies: Sanofi Aventis; Advisory / Consultancy, Travel / Accommodation / Expenses: WCG Oncology; Research grant / Funding (institution), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Menarini Silicon; Advisory / Consultancy, Travel / Accommodation / Expenses: OncLive Insights; Advisory / Consultancy, Travel / Accommodation / Expenses: Physician Education Resource; Research grant / Funding (institution): Illumina; Research grant / Funding (institution): Innocrin Pharma; Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Research grant / Funding (institution): Epic Sciences; Research grant / Funding (institution): ThermoFisher; Travel / Accommodation / Expenses: Clovis Oncology; Travel / Accommodation / Expenses: Prostate Cancer Foundation. All other authors have declared no conflicts of interest.