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

Conditions

• Prostate Cancer

Eligibility Criteria

Sex

MALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• AMG 509 — DRUG
  AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).
• Abiraterone — DRUG
  Abiraterone administered as oral tablets.
• Enzalutamide — DRUG
  Enzalutamide administered as oral tablets.

Study Details

The overall aim of the trial is to evaluate the safety, tolerability, and pharmacokinetics (PK) of AMG 509 (monotherapy and in combination with abiraterone acetate and enzalutamide) and to evaluate preliminary efficacy. As of Protocol Amendment 10 (09 July 2025), only Parts 4A expansion, 6, and 7 are open to accrual.

Key Dates

Start date

Mar 4, 2020

Status verified

May 2026

Primary completion

Mar 22, 2030

Completion

Mar 21, 2032

Study Design

Enrollment

479 participants (estimated)

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• 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 maximum tolerated dose (MTD) of AMG 509 using a Bayesian logistic regression model (BLRM; Neuenschwander et al, 2008). Recommended phase 2 dose (RP2D) may be identified based on emerging safety, efficacy, 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.
• 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. 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.
• 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 no, or 1-2 prior NHTs (may have been given for hormone-sensitive prostate cancer \[HSPC\]) and no prior taxanes (unless administered in HSPC setting). 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.
• 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 no or 1 to 2 prior NHTs given in any disease setting depending on the part (dose-expansion phase: prior therapies including at least 1 prior NHT and either 0 or 1 prior poly-ADP ribose polymerase \[PARP\] inhibitor), at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone acetate (Part 4A) or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B.
• Experimental: Part 5: AMG 509 IV Monotherapy in Outpatient Setting
  Part 5 will evaluate the safety and tolerability of AMG 509 IV dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes, when administered in outpatient infusion centers. The Part 5 dosing regimen and schedule was selected based on emerging data and dose level review team (DLRT) recommendations and will utilize the doses explored in Part 1 dose-expansion phase.
• Experimental: Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate
  Part 6 will evaluate the preliminary efficacy, safety, tolerability, and PK of AMG 509 (alone or in combination with abiraterone acetate) for participants with mCRPC who have progressed on only 1 prior NHT (prior exposure to ≤ 6 cycles of taxane is allowed in mHSPC setting) and who have Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 measurable disease. Part 6 dosing regimen has been previously determined as safe and tolerable and is aligned with the dosing schedule for Parts 3 and 4A expansion.
• Experimental: Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate
  Part 7 will only include participants from China. This part will evaluate safety and tolerability of AMG 509 IV dosing in participants who have been previously treated with NHT and 1 to 2 prior taxanes. Part 7 dosing regime will first be enrolled to dose level-1 (1.0 mg target dose) and if tolerated and if DLRT determines it is safe to escalate to the MTD/RP2D, 1.5 mg every 2 weeks (Q2W) dosing regimen may be explored. If the RP2D is safe and tolerable and once AMG 509 monotherapy dose confirmation is complete, a cohort of participants to receive AMG 509 combination therapy with abiraterone acetate may be initiated.

Primary Outcome Measure

Parts 1-5 and 7: Incidence of Treatment-emergent Adverse Events [ Time Frame: 3 years ]

Central Contacts

• Amgen Call Center
  866-572-6436
  [email protected]

Locations (25)

Find similar trials in Duarte, CA

Related Studies

• [18F]-Fluoro-2-Deoxy-D-Glucose and -[18F] Dihydro-Testosterone Pet Imaging in Patients With Progressive Prostate Cancer
  Recruiting · Memorial Sloan Kettering Cancer Center · Basking Ridge, New Jersey
• Active Surveillance for Cancer of the Prostate (ASCaP)
  Recruiting · Jonsson Comprehensive Cancer Center · Los Angeles, California
• Postoperative or Salvage Radiotherapy (RT) for Node Negative Prostate Cancer Following Radical Prostatectomy
  Recruiting · Proton Collaborative Group · Little Rock, Arkansas
• Hypo-fractionated Radiation Therapy With or Without Androgen Suppression for Intermediate Risk Prostate Cancer
  PHASE3 · Recruiting · Proton Collaborative Group · Scottsdale, Arizona