Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer

N
Nabil Adra, MD

Primary Investigator

Administratively Closed
18 years and older
Male
Phase 1
464 participants needed
1 Location

Overview

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

Eligibility

You may be eligible for this study if you meet the following criteria:

  • Conditions:
    Prostate Cancer
  • Age: 18 Years
  • Gender: Male

Inclusion Criteria:
  • Parts 1, 2, and 5: Participants with histologically or cytologically confirmed(mCRPC) who are refractory to a noveldrogen therapy (abiraterone acetate and/or enzalutamide, apalutamide, ordarolutamide) and have failed at least 1 (but not more than 2) taxane regimensuding for metastatic hormone-sensitive prostate cancer (mHSPC) (or who are deemeddically unsuitable to be treated with a taxane regimen or have actively refusedwith a taxane regimen). Note: A taxane regimen is defined as a minimumure of 2 cycles of a taxane.
    1. Dose exploration phase: Novel antiandrogen therapy must have been given fordisease.
    2. Dose expansion phase: participants must not have had more than 2 NHTs and 2gimens in any setting, and an additional up to 2 other systemicwed (eg, anti-PD1, PARP inhibitors, radioligandherapies, sipuleucel-T, experimental agents) Note: Combinations are consideredystemic anti-cancer treatment.
  • Parts 4A and 4B:
    1. Participants with histologically or cytologically confirmed mCRPC who haveved no or 1 prior NHT (given in any disease setting), and no or 1 taxane(given for hormone sensitive prostate cancer).
    2. 4A: Participants planning to receive abiraterone acetate for the first time(participants who received prior abiraterone acetate are not eligible).
    3. 4B: Participants planning to receive enzalutamide for the first time(participants who received prior enzalutamide/apalutamide or daralutamide are notgible).
  • Part 4D:
    1. Participants with histologically or cytologically confirmed mCRPC who have received1 prior NHT (abiraterone acetate, enzalutamide, apalutamide, or darolutamide)given in any disease setting and who are deemed suitable to receive docetaxel for the
  • Participants must have undergone bilateral orchiectomy or be on continuous
    androgen-deprivation therapy with a gonadotropin releasing hormone (GnRH) agonist orgonist.
  • 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 at1 week apart.
    2. nodal or visceral progression as defined by Response Evaluation Criteria in SolidTumors (RECIST) 1.1 with PCGW3 modifications.
    3. appearance of 2 or more new lesions in bone scan.
  • Eastern Cooperative Oncology Group 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 supportwithin 7 days from screening assessment); except Part 4D: absoluteutrophil count > 1.5 x 10^9/L.
      2. platelet count >= 75 x 10^9/L (without platelet transfusion within 7 daysg assessment).
      3. hemoglobin >= 9 g/dL (90 g/L) (without blood transfusion within 7 days fromg assessment).
    2. Renal function:
      1. estimated glomerular filtration rate based on Modification of Diet in RenalDisease calculation >= 30 ml/min/1.73 m^2.
    3. Hepatic function:
      1. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 xupper limit of normal (ULN) (or < 5 x ULN for participants with livervolvement); except Part 4D: AST/alkaline phosphatase (ALP) < 2.5 x ULN andALP ≤ 1.5 x ULN.
      2. total bilirubin (TBL) < 1.5 x ULN (or < 2 x ULN for participants with liver).
    4. Cardiac function:
      1. left ventricular ejection fraction > 50% (2-D transthoracic echocardiogram[ECHO] is the preferred method of evaluation; multi-gated acquisition scanble if ECHO is not available).
      2. Baseline electrocardiogram (ECG) QTcF <= 470 msec.
Exclusion Criteria:
  • Pathological finding consistent with pure small cell, neuroendocrine carcinoma of they other histology different from adenocarcinoma.
  • Radiation therapy within 4 weeks of first dose (or local or focal radiotherapy within2 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 isdiographic evidence of improvement upon the completion of CNS-directed therapy andvidence of interim progression between the completion of CNS-directed therapy andhe screening radiographic study.
  • Participants with symptoms and/or clinical signs and/or radiographic signs thatdicate an acute and/or uncontrolled active systemic infection within 7 days prior tohe first dose of investigational product administration.
  • Confirmed history or current autoimmune disease or other diseases resulting inunosuppression or requiring permanent immunosuppressive therapy.
  • History of arterial or venous thrombosis (eg, stroke, transient ischemic attack,ulmonary embolism, or deep vein thrombosis); for arterial thrombosis within 12 monthsAMG 509 initiation; for venous thrombosis, 6 months and stable on anti-coagulation.
  • Myocardial infarction and/or symptomatic congestive heart failure (New York HeartAssociation > class II) within 12 months of first dose of AMG 509 with the exceptionhemia or non-ST segment elevation myocardial infarction controlled with stentd confirmed by a cardiologist more than 6 months prior to first dose of AMG 509.
  • Any anti-cancer therapy or immunotherapy within 4 weeks of start of first dose, notuding 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.

Updated on 16 May 2024. Study ID: 20180146, CTO-20180146, 2001999530

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