Purpose

Evaluate the safety and tolerability of AMG 509 in adult subjects and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Male
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Parts 1, 2: Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone and/or enzalutamide, apalutamide, darolutamide, bicalutamide, or equivalent) 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). 1. Dose exploration phase: novel antiandrogen therapy must have been given for treatment of metastatic disease. 2. Dose expansion phase: progression on novel antiandrogen therapy may have occurred in the non-metastatic or metastatic setting. - Parts 4A and 4B: 1. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) given for hormone-sensitive prostate cancer (HSPC) or non-metastatic CRPC and have failed up to 1 taxane regimen for HSPC (or who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen). 2. 4A: Participants planning to receive abiraterone for the first time (participants who received prior abiraterone are not eligible). 3. 4B: Participants planning to receive enzalutamide for the first time (participants who received prior enzalutamide/apalutamide or daralutamide are not eligible). - Parts 3 a. Participants with histologically or cytologically confirmed mCRPC who are refractory to a novel antiandrogen therapy (eg, abiraterone, enzalutamide, apalutamide, darolutamide, bicalutamide or equivalent) given in any disease setting and who are deemed medically unsuitable to be treated with a taxane regimen or have actively refused treatment with a taxane regimen. - Participants must have undergone bilateral orchiectomy or be on continuous androgen-deprivation therapy (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 Prostate Cancer Working Group 3 (PCWG3) criteria: 1. PSA level >= 1 ng/mL that has increased on at least 2 successive occasions at least 1 week apart. 2. nodal or visceral progression as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 with PCGW3 modifications. 3. appearance of 2 or more new lesions in bone scan. - Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. - Adequate organ function, defined as follows: 1. Hematological function: 1. absolute neutrophil count >= 1 x 10^9/L (without growth factor support within 7 days from screening assessment). 2. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 days from screening assessment). 3. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days from screening assessment). 2. Renal function: 1. estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation >= 30 ml/min/1.73 m^2. 3. Hepatic function: 1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN) (or < 5 x ULN for participants with liver involvement). 2. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver metastases). 4. Cardiac function: 1. left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram [ECHO] is the preferred method of evaluation; multi-gated acquisition scan is acceptable if ECHO is not available). 2. Baseline electrocardiogram (ECG) QTcF <= 470 msec.

Exclusion Criteria

  • 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). - Untreated central nervous system (CNS) metastases or leptomeningeal disease. Participants with a history of treated CNS metastases are eligible if there is radiographic evidence of improvement upon the completion of CNS-directed therapy and no evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. - Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. - History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 months of AMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation. - Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association > class II) within 12 months of first dose of AMG 509. - Any anticancer therapy or immunotherapy within 4 weeks of start of first dose, not including luteinizing hormone-releasing hormone (LHRH)/GnRH analogue (agonist/antagonist). Participants on a stable bisphosphonate or denosumab regimen for >= 30 days prior to enrollment are eligible.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part 1: AMG 509 Intravenous (IV) Monotherapy
Part 1 will evaluate AMG 509 in participants with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with novel hormonal therapy (NHT) and 1 to 2 prior taxanes. The dose exploration phase of the study will estimate the MTD of AMG 509 using a Bayesian logistic regression model (BLRM; Neuenschwander et al, 2008). RP2D may be identified based on emerging safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) data, as well as patient experience prior to reaching an MTD. Alternative dosing schedule(s) (including a third step dose) may be explored based on emerging efficacy, safety, PK data and patient experience. During the dose expansion phase, individual cohorts of participants from China will be enrolled with a safety lead-in at 1 dose level below the MTD or RP2D followed by evaluation at the MTD or RP2D to confirm the safety, tolerability, MTD and/or RP2D of AMG 509 in Chinese participants.
  • Drug: AMG 509
    AMG 509 administered as an IV infusion (Parts 1, 3 and 4) or SC injection (Part 2).
Experimental
Part 2: AMG 509 Subcutaneous (SC) Monotherapy
Part 2 will explore the safety, tolerability, and PK of AMG 509 SC dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes. The dose exploration phase of Part 2 of the study will estimate the MTD of AMG 509 SC using a BLRM (Neuenschwander et al, 2008). Recommended phase 2 dose for SC monotherapy may be identified based on emerging safety, efficacy, PK, and PD data, as well as patient experience prior to reaching an MTD.
  • Drug: AMG 509
    AMG 509 administered as an IV infusion (Parts 1, 3 and 4) or SC injection (Part 2).
Experimental
Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment
Part 3 will explore AMG 509 in participants with mCRPC who have received 1 prior NHT. This dose expansion will be conducted to confirm safety, PK, and PD of AMG 509 at the MTD or RP2D determined in Part 1 dose exploration, and to obtain further safety and efficacy data and correlative biomarker analysis.
  • Drug: AMG 509
    AMG 509 administered as an IV infusion (Parts 1, 3 and 4) or SC injection (Part 2).
Experimental
Part 4: AMG 509 IV Combination Therapy
Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received 1 prior NHT, at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A) or enzalutamide (Part 4B). Part 4 consists of a dose exploration phase and a dose expansion phase. This dose exploration study will estimate the MTD and/or RP2D of AMG 509 in combination with abiraterone or enzalutamide using a modified toxicity probability interval design.
  • Drug: AMG 509
    AMG 509 administered as an IV infusion (Parts 1, 3 and 4) or SC injection (Part 2).
  • Drug: Abiraterone
    Abiraterone administered as oral tablets.
  • Drug: Enzalutamide
    Enzalutamide administered as oral tablets.

Recruiting Locations

Tulane Medical Center
New Orleans, Louisiana 70112

More Details

Status
Recruiting
Sponsor
Amgen

Study Contact

Amgen Call Center
866-572-6436
medinfo@amgen.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.