Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC

Inclusion Criteria

• •All Parts
• •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
• •Subjects must have undergone bilateral orchiectomy or must be on continuous 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
• •appearance of 2 or more new lesions in bone scan
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
• •Life expectancy \>/= 6months
• •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 acapatamab
• •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