Safety, Tolerability, Pharmacokinetics, and Efficacy of Acapatamab in Subjects With mCRPC
- Conditions
- Metastatic Castration-resistant Prostate Cancer / Prostate Cancer
- Registration Number
- JPRN-jRCT2031200362
- Lead Sponsor
- ocal Contact
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Complete
- Sex
- Male
- Target Recruitment
- 212
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 5. 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
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1
7. Life expectancy >/= 6months
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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1.Number of participants with dose-limiting toxicity [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study<br>2.Number of participants with treatment-emergent adverse events [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study<br>3.Number of participants with treatment-related adverse events [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study<br>4.Number of participants with clinically significant changes in vital signs [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study<br>5.Number of participants with clinically significant changes in electrocardiogram (ECG) [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study<br>6.Number of participants with clinically significant changes in clinical laboratory tests [ Time Frame: Up to 3 years ]<br> Parts 1, 2, 3, 4, 5, and 6 of the study
- Secondary Outcome Measures
Name Time Method