Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
Acapatamab, HALF-LIFE EXTENDED (HLE) BITE, mCRPC, Metastatic Castration-resistant Prostate Cancer, 68, Gallium (68Ga)-prostate-specific membrane, antigen (PSMA)-11 positron emission, tomography(PET)/computed tomography (CT), and, 18, F-fluorodeoxyglucose (FDG) PET/CT, based response evaluation, Bispecific T cell Engager, BITE
Brief summary
This is a master protocol designed to evaluate the safety and efficacy of investigational therapies in participants with metastatic castration-resistant prostate cancer (mCRPC).
Detailed description
This is a master protocol designed to evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and efficacy of Acapatamab, in combination with enzalutamide, abiraterone, or the PD1 inhibitor AMG 404, AMG 404 monotherapy, as well as Acapatamab monotherapy, in participants with metastatic castration-resistant prostate cancer (mCRPC).
Interventions
DRUGAcapatamab
Acapatamab will be administered as an intravenous (IV) infusion.
DRUGEnzalutamide
Enzalutamide will be administered orally.
DRUGAbiraterone
Abiraterone will be administered orally.
DRUGAMG 404
AMG 404 will be administered as an intravenous (IV) infusion.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
All parts Inclusion Criteria: * ≥ 18 years of age (or legal adult age within country) * Subject has provided informed consent prior to initiation of any study-specific activities/procedures * Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate * Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist (testosterone ≤ 50 ng/dL (or 1.7 nmol/L))
Exclusion criteria
* Central nervous system (CNS) metastases or leptomeningeal disease * History or presence of clinically relevant CNS pathology * Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy * Myocardial infarction, uncontrolled hypertension, unstable angina, cardiac arrhythmia requiring medication, and/or symptomatic congestive heart failure (New York Heart Association \> class II) within 12 months * Prior treatment with a taxane for mCRPC * Major surgery and/or Radiation within 4 weeks * History or evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection unless agreed upon with medical monitor and meeting the following criteria: * Negative test for SARS-CoV-2 RNA by real time polymerase chain reaction (RT-PCR) within 72 hours of first dose of Acapatamab (or AMG 404 in Part 3) * No acute symptoms of COVID-19 disease within 10 days prior to first dose of Acapatamab (or AMG 404 in Part 3) (counted from day of positive test for asymptomatic subjects) Prior/Concurrent Clinical Study Experience * Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded with the exception of investigational scans. Subprotocol A only: Inclusion criteria • Subjects planning to receive enzalutamide for the first time for mCRPC
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose exploration only: Number of participants who experience dose limiting toxicities (DLTs) | Up to 3 years | The analysis of all endpoints, unless noted otherwise, will be conducted on the Safety Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab. The analysis of dose-limiting toxicity (DLT) will be conducted on the DLT Analysis Set defined as all subjects that are enrolled and receive at least 1 dose of Acapatamab with an evaluable DLT endpoint. If a single subject experiences more than 1 DLT it will be counted as 1. The DLT endpoint is evaluable if either: 1\) the subject experiences a DLT; or 2) the subject does not experience a DLT after receiving all planned doses within the 28-day DLT window in cycle 1. |
| Number of participants who experience one or more treatment-emergent adverse events (TEAEs) | Up to 3 years | — |
| Number of participants who experience one or more treatment-related adverse events | Up to 3 years | — |
| Number of participants who experience a clinically significant change in vital signs | Up to 3 years | — |
| Number of participants who experience a clinically significant change in clinical laboratory tests | Up to 3 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to progression | Up to 3 years |
| Time to subsequent therapy | Up to 3 years |
| Maximum plasma concentration (Cmax) | Up to 3 years |
| Minimum plasma concentration (Cmin) | Up to 3 years |
| Objective response rate per response evaluation criteria in solid tumors (RECIST) 1.1 with prostate cancer working group 3 (PCWG3) modifications | Up to 3 years |
| Number of participants who experience circulating tumor cell (CTC) response | Up to 3 years |
| Number of participants who experience prostate-specific antigen (PSA) response rate | Up to 3 years |
| Duration of response | Up to 3 years |
| Area under the concentration-time curve (AUC) | Up to 3 years |
| Change from baseline in prostate-specific membrane antigen (PSMA)-negative disease burden assessed using 18F-fluorodeoxyglucose (F-FDG) positron emission tomography/computed tomography (PET/CT) | Baseline to 3 years |
| Time to symptomatic skeletal events | Up to 3 years |
| Concentration of alkaline phosphatase | Up to 3 years |
| Concentration of lactate dehydrogenase (LDH) | Up to 3 years |
| Concentration of hemoglobin | Up to 3 years |
| Neutrophil-to-lymphocyte ratio | Up to 3 years |
| Concentration of N-telopeptide in the urine | Up to 3 years |
| Change from baseline in prostate-specific membrane antigen (PSMA)-positive tumor burden assessed using gallium (GA) 68-labelled PSMA-11 positron emission tomography/computed tomography (PET/CT) | Baseline up to 3 years |
| Accumulation ratio based on area under the concentration-time curve (AUC) | Up to 3 years |
| Half-life (t1/2) | Up to 3 years |
| Overall survival (OS) | Up to 3 years |
| Progression-free survival | Up to 3 years |
Countries
Australia, Denmark, Spain, Sweden, United Kingdom, United States
Outcome results
None listed