Metastatic Castration-resistant Prostate Cancer MedDRA version: 21.1 Level: LLT Classification code 10076506 Term: Castration-resistant prostate cancer System Organ Class: 100000004864
Conditions
Interventions
Product Name: AMG 160
Product Code: AMG 160
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: Pending
Current Sponsor code: AMG 160
Other descriptive name: AMG 160
Conce
Sponsors
Amgen
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: All Subprotocols - Subjects with mCRPC with histologically or cytologically confirmed adenocarcinoma of the prostate without pure neuroendocrine differentiation or small cell features - Subjects should have undergone bilateral orchiectomy or should be on continuous androgen deprivation therapy with a gonadotropin releasing hormone agonist or antagonist. - Total serum testosterone should be = 50 ng/dL (or 1.7 nmol/L) - Eastern Cooperative Oncology Group (ECOG) performance status of 0 – 1 - Life expectancy of > 3 months - Adequate organ function, defined as follows: • absolute neutrophil count = 1.5 x 10^9/L (without growth factor support within 7 days from screening assessment) • platelet count = 100 x 10^9/L (without platelet transfusion within 7 days from screening assessment) • hemoglobin > 9 g/dL (90 g/L) (subprotocol A & C) / > 10 g/dL (100g/L) (subprotocol B) (without blood transfusion within 7 days from screening assessment) • estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation = 30 mL/min/1.73 m2 • AST and ALT 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available) - Baseline electrocardiogram (ECG) QTc = 470 msec Subprotocol A & B only - Subjects planning to receive enzalutamide (subprotocol A) / abiraterone (subprotocol B) for the first time for mCRPC (subjects who received prior enzalutamide (subprotocol A) / abiraterone (subprotocol B) are not eligible). Subprotocol C only - Subjects who are refractory to a novel antiandrogen therapy (abiraterone, apalutamide, and/or enzalutamide) given for metastatic or non-metastatic prostate cancer. Subjects must be ineligible for or refuse taxane therapy. - Evidence of progressive disease, defined as 1 or more PCWG3 criteria: • PSA level of at least 1 ng/mL that has risen 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 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 65 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 64
Exclusion criteria
Exclusion criteria: All Subprotocols - Pathological finding consistent with pure small cell, neuroendocrine carcinoma of the prostate or any other histology different from adenocarcinoma - CNS metastases/leptomeningeal disease - Symptomatic peripheral sensory/motor neuropathy =grade3 - History/presence of clinically relevant CNS pathology - Confirmed history/current autoimmune disease or other diseases resulting in permanent immunosuppression/requiring permanent immunosuppressive therapy - Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials (Subprotocol A&B) /active fungal, bacterial, viral, or other infection requiring systemic therapy (Subprotocol C) within 7days of dosing - History/evidence of inflammatory bowel disease or any other GI disorder causing chronic nausea, vomiting, or diarrhea - History of arterial/venous thrombosis within 12months of 1st dose - Myocardial infarction, uncontrolled hypertension (Subprotocol A&C), unstable angina, cardiac arrhythmia requiring medication, &/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months (Subprotocol A&B) /within 6months (Subprotocol C) of 1st dose of AMG 160 - Unresolved toxicities from prior anti-tumor therapy not having resolved to CTCAE version 5.0 grade 1, except for alopecia or toxicities that are stable and well-controlled & there is agreement to allow by both the investigator & sponsor - Known HIV infection, hepatitis C or hepatitis B infection - History of other malignancy within the past 2years, with the following exceptions: • Malignancy treated with curative intent & with no known active disease present for =3 years before enrollment and felt to be at low risk for recurrence by treating physician • Adequately treated non-melanoma skin cancer/lentigo maligna without evidence of disease • Adequately treated urothelial papillary noninvasive carcinoma/carcinoma in situ - Prior treatment with a taxane for mCRPC - Radiation therapy within 4weeks of 1st dose (or local or focal radiotherapy within 2 weeks) - Any anticancer therapy/immunotherapy within 4 weeks (2 weeks Subprotocol C) of start of 1st dose, not including LHRH/GnRH analogue. Subjects on a stable bisphosphonate/denosumab regimen for =30 days prior to enrollment are eligible - Prior PSMAxCD3 bispecific therapy (not subprotocol C part 3) - Requiring chronic systemic corticosteroid therapy/any other immunosuppressive therapies. Low dose corticosteroids permitted - Prior major surgery within 4 weeks of 1st dose - Currently receiving treatment in another investigational device/drug study, or <4 weeks since ending treatment on another investigational device or drug study - Male subjects with a female partner of childbearing potential/pregnant partner who are unwilling to practice sexual abstinence/use contraception during treatment and for an additional 4 months (Subprotocol A&B) /8 months (Subprotocol C) after the last dose - Male subjects unwilling to abstain from donating sperm during treatment and for an additional 4 months (Subprotocol A&B) /8 months (Subprotocol C) after the last dose - Subject has known sensitivity to any of the products (or components) to be administered during dosing - Subject likely to not be available to complete all protocol-required study visits/procedures, &/or to comply with all required study procedures - History/evidence of any other clinically significant disorder, condition or disease (except for those outlined above) that, in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: All subprotocols To evaluate the safety, tolerability, and maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of investigational therapies in subjects with metastatic castration-resistant prostate cancer (mCRPC) Subprotocol C Part 3 only •To evaluate preliminary anti-tumor activity of AMG 404 monotherapy;Secondary Objective: All subprotocols •To evaluate preliminary anti-tumor activity of investigational therapies in subjects with mCRPC •To characterize the pharmacokinetics (PK) of investigational therapies in subjects with mCRPC Subprotocol C part 3 only • Safety: To evaluate the safety and tolerability of AMG 404 monotherapy • Efficacy: To evaluate anti-tumor activity of AMG 404 monotherapy with additional measures;Primary end point(s): All subprotocols • dose-limiting toxicities (DLTs) • treatment-emergent and treatment-related adverse events • changes in vital signs, and clinical laboratory tests Subprotocol C Part 3 • objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications • circulating tumor cell (CTC) response (CTC0 and CTC conversion) • prostate-specific antigen (PSA) response;Timepoint(s) of evaluation of this end point: 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 AMG 160 (or AMG 404 in Parts 1 and 2 and at least 1 dose of AMG 404 in Part 3 - Subprotocol C). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): All subprotocols • objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with Prostate Cancer Working Group 3 (PCWG3) modifications • circulating tumor cell (CTC) response (CTC0 and CTC conversion) • prostate-specific antigen (PSA) response • duration of response (CTC, PSA, conventional radiographic) • overall survival (OS) • progression-free survival (radiographic, PSA, clinical) • time to progression (radiographic, PSA) • time to subsequent therapy • prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) PET/CT based response evaluation • other PCWG3-recommended endpoints (time to symptomatic skeletal events, alkaline phosphatase [total, bone], lactate dehydrogenase [LDH], hemoglobin, neutrophil to-lymphocyte ratio, urine N-telopeptide) • PK parameters including, but not limited to, maximum serum concentration (Cmax), minimum serum concentration (Cmin), area under the concentration-time curve (AUC) over the dosing interval, accumulation, and half-life (t1/2) Subprotocol C Part 3 only • treatment-emergent adverse events • treatment-related adverse events • changes in vital signs, and clinical laboratory tests;Timepoint(s) of evaluation of this end point: 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 AMG 160 (or AMG 404 in Parts 1 and 2 and at least 1 dose of AMG 404 in Part 3 - Subprotocol C). | — |
Countries
Australia, Canada, Denmark, Germany, Italy, Netherlands, Sweden, United States
Contacts
Public ContactMedical Information
Amgen GmbH
Outcome results
None listed