Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 160 in Subjects With mCRPC

• ClinicalTrials.gov Identifier: NCT03792841
• Recruitment Status: Recruiting
• First Posted: January 3, 2019
• Last Update Posted: February 16, 2021
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Study Description

Brief Summary:

A study to evaluate the safety and tolerability of AMG 160 and in combination with pembrolizumab in adult subjects with metastatic castration-resistant prostate cancer (mCRPC), and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Condition or disease	Intervention/treatment	Phase
Metastatic Castration-resistant Prostate Cancer; Prostate Cancer	Drug: AMG 160; Drug: Pembrolizumab; Drug: Etanercept; Drug: Immunomodulating Agent	Phase 1

Detailed Description:

This is a phase I, first-in-human study to evaluate the safety and tolerability of AMG 160; a half-life extended (HLE) bispecific T-cell engager (BiTE®) antibody construct, alone and in combination with pembrolizumab in subjects with metastatic castration-resistant prostate cancer.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 288 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen Half-life Extended Bispecific T-cell Engager AMG 160 in Subjects With Metastatic Castration-resistant Prostate Cancer
• Actual Study Start Date: February 5, 2019
• Estimated Primary Completion Date: January 17, 2025
• Estimated Study Completion Date: January 17, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: AMG 160 Treatment; Part 1: AMG 160 is administered intravenously at different dose levels.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy
Experimental: AMG 160 + Pembrolizumab; Part 2: AMG 160 is administered intravenously at different dose levels. Pembrolizumab will be administered intravenously.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy; Drug: Pembrolizumab; Combined with AMG 160 for investigational treatment of mCRPC; Other Name: PD-1 inhibitor
Experimental: AMG 160 + Etanercept Prophylaxis; Part 3: AMG 160 is administered intravenously at RP2D/MTD levels. Etanercept will be administered subcutaneously in cycle 1 only.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy; Drug: Etanercept; Prophylaxis for AMG 160-related cytokine release syndrome.; Other Name: TNF-alpha inhibitor
Experimental: AMG 160 24 hr monitoring; Part 4: AMG 160 is administered intravenously at RP2D/MTD with 24-hour monitoring.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy
Experimental: AMG 160 Outpatient Cohort; Part 5: AMG 160 is administered intravenously at RP2D/MTD in an outpatient setting with 8-hour monitoring.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy
Experimental: AMG 160 + Immunomodulating Agent; Part 6: AMG 160 is administered intravenously at RP2D/MTD levels. Immunomodulating agent will be administered orally.	Drug: AMG 160; Investigational immunotherapy for the treatment of metastatic castration-resistant prostate cancer; Other Name: PSMA Targeted Therapy; Drug: Immunomodulating Agent; Prophylaxis for AMG 160-related cytokine release syndrome; Other Name: Immunomodulator

Outcome Measures

Primary Outcome Measures :

1. Number of participants with dose-limiting toxicity [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
2. Number of participants with treatment-emergent adverse events [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
3. Number of participants with treatment-related adverse events [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
4. Number of participants with clinically significant changes in vital signs [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
5. Number of participants with clinically significant changes in electrocardiogram (ECG) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
6. Number of participants with clinically significant changes in clinical laboratory tests [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study

Secondary Outcome Measures :

1. Subject incidence of changes in pharmacokinetics - maximum serum concentration (Cmax) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
2. Objective response (OR) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
3. Prostate-specific antigen (PSA) response [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
4. Duration of response (DOR) (radiographic and PSA) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
5. Change in time to progression (radiographic and PSA) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
6. 1, 2 and 3-year overall survival (OS) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
7. Other PCWG3-recommended endpoints - time to symptomatic skeletal events [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
8. Subject incidence of changes in pharmacokinetics - minimum serum concentration (Cmin) [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
9. Subject incidence of changes in pharmacokinetics - area under the concentration-time curve (AUC) over the dosing interval [ Time Frame: Up to 3 years ]
   Parts 1, 2, 3, 4, 5, and 6 of the study
10. Subject incidence of changes in pharmacokinetics - administration including accumulation following multiple dosing [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
11. Subject incidence of changes in pharmacokinetics - half-life [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
12. Other PCWG3-recommended endpoints - lactate dehydrogenase [LDH] [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
13. Other PCWG3-recommended endpoints - hemoglobin [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
14. Other PCWG3-recommended endpoints - neutrophil-to-lymphocyte ratio [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
15. Other PCWG3-recommended endpoints - urine N-telopeptide [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study
16. Other PCWG3-recommended endpoints alkaline phosphatase [total, bone] [ Time Frame: Up to 3 years ]
    Parts 1, 2, 3, 4, 5, and 6 of the study

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

All Parts

Inclusion Criteria:

• Subject has provided informed consent prior to initiation of any study-specific activities/procedures
• Subjects with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (abiraterone, enzalutamide, and/or apalutamide) and have failed at least 1 (but not more than 2) taxane regimens (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). Progression on novel antiandrogen therapy may have occurred in the non-metastatic CRPC setting
• Subject should have undergone bilateral orchiectomy or should be on continuous androgen-deprivation therapy (ADT) with a gonadotropin-releasing hormone (GnRH) agonist or antagonist
• Total serum testosterone </= 50 ng/dL or 1.7 nmol/L
• Evidence of progressive disease, defined as 1 or more PCWG3 criteria:

PSA level >/=1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart, nodal or visceral progression as defined by RECIST 1.1 with PCGW3 modifications, and/or appearance of 2 or more new lesions in bone scan

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• Life expectancy >/=6 months

Exclusion Criteria:

• Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone agonist (LHRH)/GnRH analogue (agonist/antagonist). Subjects on a stable bisophosphonate or denosumab regimen for >/= 30 days prior to randomization are eligible
• Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment)
• Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
• Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study
• Needing chronic systemic corticosteroid therapy (prednisone > 10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-tumor necrosis factor alpha [TNF alpha] therapies) unless stopped 7 days prior to start of first dose
• Myocardial infarction, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 160

Part 2 only:

• Subjects on a prior PD-1 or PD-L1 inhibitor who experienced a Grade 3 or higher immune-related adverse event prior to first day of dosing
• History or evidence of interstitial lung disease or active, non-infectious pneumonitis

Part 3 only:

-Evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product

Part 6 only:

Subjects are excluded from this cohort if any of the following additional criteria apply:

• Subjects taking strong OAT3 inhibitors (eg, probenecid) or adjust the dosing to 1 mg PO QD.
• Subjects with latent or active tuberculosis at screening

Contacts and Locations

Contacts

Contact: Amgen Call Center; 866-572-6436; medinfo@amgen.com

Locations

United States, California

Research Site; Recruiting

Duarte, California, United States, 91010

Research Site; Recruiting

Los Angeles, California, United States, 90095

United States, Georgia

Research Site; Recruiting

Atlanta, Georgia, United States, 30322

United States, Indiana

Research Site; Recruiting

Indianapolis, Indiana, United States, 46202

United States, New York

Research Site; Recruiting

New York, New York, United States, 10065

Australia, New South Wales

Research Site; Recruiting

Camperdown, New South Wales, Australia, 2050

Research Site; Recruiting

Randwick, New South Wales, Australia, 2031

Australia, Victoria

Research Site; Recruiting

Melbourne, Victoria, Australia, 3000

Austria

Research Site; Recruiting

Salzburg, Austria, 5020

Research Site; Recruiting

Wien, Austria, 1020

Research Site; Recruiting

Wien, Austria, 1090

Belgium

Research Site; Recruiting

Bruxelles, Belgium, 1200

Research Site; Recruiting

Gent, Belgium, 9000

France

Research Site; Recruiting

Villejuif Cedex, France, 94805

Japan

Research Site; Recruiting

Yokohama-shi, Kanagawa, Japan, 232-0024

Research Site; Recruiting

Chiba, Kashiwa-shi, Japan, 277-8577

Netherlands

Research Site; Recruiting

Rotterdam, Netherlands, 3015 GD

Singapore

Research Site; Recruiting

Singapore, Singapore, 119074

Research Site; Recruiting

Singapore, Singapore, 169610

Sponsors and Collaborators

Amgen

Investigators

• Study Director: MD; Amgen

More Information

Additional Information:

AmgenTrials clinical trials website 

• Responsible Party: Amgen
• ClinicalTrials.gov Identifier: NCT03792841
• Other Study ID Numbers: 20180101
• First Posted: January 3, 2019
• Last Update Posted: February 16, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe, or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• URL: https://www.amgen.com/datasharing

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:

AMG 160; HLE-BiTE®; mCRPC; Metastatic Castration-resistant Prostate Cancer; Prostate cancer; PSMA; BiTE®; Bispecific T-Cell engager; Immunotherapy; Immuno-oncology; Immunooncology; Solid tumor; PSMA Targeted Therapy

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Etanercept; Pembrolizumab; Immunologic Factors; Antineoplastic Agents, Immunological; Antineoplastic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Immunosuppressive Agents