Metastatic Castration-resistant Prostate Cancer / Prostate Cancer
Conditions
Interventions
Experimental: Part 1 Dose-exploration: acapatamab treatment
Part 1 dose-exploration: acapatamab is administered intravenously. The dose-exploration phase of the study will estimate the MTD of acapata
Sponsors
Local Contact
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Subject has provided informed consent prior to initiation of any study specific activities/procedures 2. 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 3. Subjects must have undergone bilateral orchiectomy or must be on continuous ADT with a gonadotropin releasing hormone (GnRH) agonist or antagonist 4. Total serum testosterone /= 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 - appearance of 2 or more new lesions in bone scan 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1 7. Life expectancy >/= 6months
Exclusion criteria
Exclusion criteria: 1. 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 2. Prior PSMA-targeted therapy (subjects on prior therapy may be eligible if discussed with Amgen medical monitor prior to enrollment) 3, Central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression 4. Active autoimmune disease or any other diseases requiring immunosuppressive therapy while on study 5. 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 6. 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 acapatamab Part 2 only: 7. 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 8. History or evidence of interstitial lung disease or active, non-infectious pneumonitis Part 3 only: 9. 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: 10. Use of any known inhibitors or inducers of drug-metabolizing enzymes within 30 days prior to study start and through start of cycle 3. 11. Use of the following components of the CYP phenotyping cocktail (midazolam HCl, warfarin sodium, vitamin K, omeprazole, and dextromethorphan HBr) within 14 days prior to cycle 1 day 1.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 1. Maximum serum concentration (Cmax) of acapatamab [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 2. Minimum serum concentration (Cmin) of acapatamab [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 3. Area under the concentration-time curve (AUC) over the dosing interval of acapatamab [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5,and 6 of the study 4. Accumulation ratio of acapatamab [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 5. Half-life of acapatamab [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 6. Objective response (OR) [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 7. Prostate-specific antigen (PSA) response [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 8. Duration of response (DOR) (radiographic and PSA) [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study 9. Percentage of participants experiencing a response based on 68Gallium (68Ga)-prostate-specific membrane antigen (PSMA)-11 positron emission tomography (PET)/computed tomography (CT) response evaluations [Time Frame: Up to 3 years] Parts 1, 2 and 3 only. 10. Percentage of participants experiencing a response based on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) response evaluations [Time Frame: Up to 3 years] Parts 1, 2 and 3 only. 11. 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 12. Progression-free survival (PFS) (radiographic and PSA) [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study. 13. 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 14. Percentage of participants experiencing circulating tumor cells (CTC) response [Time Frame: Up to 3 years] Parts 1, 2, 3, 4, 5, and 6 of the study. CTC response defined as CTC0 (reduction of CTCs > 0 to 0) or CTC co | — |
Countries
Australia, Austria, Belgium, Canada, France, Japan, Netherlands, Singapore, Taiwan, United States
Contacts
Public ContactLocal Contact Local
Amgen K.K.
Outcome results
None listed