A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Prostate Specific Membrane Antigen (PSMA) Half Life Extended (HLE) Bispecific T-cell Engager (BiTE) AMG 160 in Subjects With Metastatic Castration Resistant Prostate Cancer (mCRPC)
- Conditions
- prostaat kankerMetastatic Castration-ResistantProstate Cancer10036958
- Registration Number
- NL-OMON52552
- Lead Sponsor
- Amgen
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 17
All parts
- Age >= 18 years at the time of signing the informed consent
- 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.
- Expansion cohort 1b only: maximum of 3 systemic therapies administered in any
prostate cancer disease setting (including chemotherapy, systemic radiotherapy,
novel hormonal, or investigational therapies, but not including ADT or bone
targeted therapies)
- Expansion cohort 1b only: subjects with baseline PSMA-positive disease
assessed by PSMA PET scan (central assessment)
- 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
Please see section 6.1 of the protocol.
All parts
- Pathological finding consistent with pure small cell, neuroendocrine
carcinoma of the prostate or any other histology different from adenocarcinoma
- Radiation therapy within 4 weeks of first dose (or local or focal
radiotherapy within 2 weeks of first dose)
- Central nervous system (CNS) metastases, leptomeningeal disease, or spinal
cord compression
- Prior major surgery within 4 weeks of first dose
- Active autoimmune disease or any other diseases requiring immunosuppressive
therapy while on study
- Presence of fungal, bacterial, viral, or other infection requiring IV
antimicrobials for management within 7 days of dosing
NOTE: Simple urinary tract infections and uncomplicated bacterial pharyngitis
are permitted if responding to active treatment and after consultation with
sponsor. Screening for chronic infectious conditions is not required.
- History of arterial or venous thrombosis (eg, stroke, transient ischemic
attack, pulmonary embolism or deep vein trombosis) within 12 months of first
dose of AMG 160
- Symptomatic peripheral sensory or motor neuropathy of grade >= 3
- History or presence of clinically relevant CNS pathology as uncontrolled
epilepsy or seizure disorder, paresis, aphasia, stroke, severe brain injuries,
dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, and
psychosis
- Myocardial infarction, unstable angina, cardia arrhythmia requiring
medication, and/or symptomatic congestive heart failure (New York Heart
Association > class II) within 12 months of first dose of AMG 160
- Unresolved toxicities from prior anti-tumor therapy not having resolved to
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1,
with the exception of alopecia or toxicities that are stable and
well-controlled AND there is agreement to allow by both the investigator and
sponsor
- History of other malignancy within the past 2 years, with the following
exception(s):
• malignancy treated with curative intent and with no known active disease
present for >= 2 years before enrollment and felt to be at low risk for
recurrence by the treating physician
• adequately treated non-melanoma skin cancer or lentigo maligna without
evidence of disease
• adequately treated urothelial papillary noninvasive carcinoma or carcinoma in
situ
- History or evidence of gastrointestinal inflammatory bowel disease
(ulcerative colitis or Crohn disease) or any other gastrointestinal disorder
causing chronic nausea, vomiting, or diarrhea (defined as >= 2 CTCAE grade 2)
- Prior PSMA-targeted therapy (subjects on prior PSMA radionuclide therapy may
be eligible if discussed with Amgen medical monitor prior to enrollment)
NOTE: subject cannot have received PSMA radionuclide therapy < 35 days prior to
enrollment if subject received < 2 cycles therapy; for each additional cycle of
therapy, an additional 30 days are required for wash out)
- Any anticancer therapy or immunotherapy within 4 weeks of start of first
dose, not including LHRH/GnRH analogue (agonist/antagonist). Subjects on a
stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment
are eligible
- Needing chronic systemic corticosteroid therapy (prednisone dose > 10 mg per
day or equivalent) or any other immunosuppressive therapies (including
anti-TNFa
Study & Design
- Study Type
- Observational invasive
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Endpoint<br /><br>• dose-limiting toxicities (DLTs)<br /><br>• treatment-emergent adverse events<br /><br>• treatment-related adverse events<br /><br>• changes in vital signs, electrocardiogram (ECG), and clinical laboratory<br /><br>tests</p><br>
- Secondary Outcome Measures
Name Time Method