What side effects are associated with this type of intervention?

Common treatments for prostate cancer include androgen deprivation therapy (ADT), abiraterone, enzalutamide, and chemotherapy agents like docetaxel and cabazitaxel. ADT can cause side effects such as hot flashes, decreased libido, fatigue, and osteoporosis. Abiraterone is associated with hypertension, hypokalemia, and liver dysfunction, while enzalutamide can lead to fatigue, falls, and peripheral edema. Chemotherapy agents like docetaxel and cabazitaxel may cause myelosuppression, neuropathy, and gastrointestinal symptoms. These treatments aim to manage the disease but come with a range of potential adverse effects that need to be monitored.

What prior FDA approvals exist?

The FDA has approved several advanced treatments for prostate cancer, particularly for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide, an androgen receptor inhibitor, has shown improved overall survival and progression-free survival in multiple trials. Abiraterone acetate, an androgen synthesis inhibitor, is another key drug that has demonstrated significant survival benefits when combined with prednisone. Additionally, radium-223, a bone-targeting radioisotope, has been approved for its ability to improve survival and delay skeletal-related events. These treatments have been pivotal in managing advanced prostate cancer, offering various mechanisms to inhibit cancer progression.

What other types of research exist?

Promising novel alternatives to AMG 509 for prostate cancer treatment in 2024 include: <ol> <li>Lutetium-177-PSMA-617: A radioligand therapy targeting PSMA-positive mCRPC, showing significant efficacy in the VISION trial.</li> <li>Pembrolizumab: An immune checkpoint inhibitor for patients with dMMR or high TMB mCRPC.</li> <li>Sipuleucel-T: An immunotherapy used earlier in the treatment course of CRPC to optimize outcomes.</li> <li>Enzalutamide and Abiraterone: Androgen receptor inhibitors used in combination with ADT for improved survival in mCRPC.</li> <li>Ra-223: A radiopharmaceutical used in combination with other agents like abiraterone or enzalutamide, particularly with osteoclast inhibitors to reduce fracture risk.</li> </ol>

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Protein Kinase Inhibitor

AMG 509 for Prostate Cancer

Q: What is the mechanism of action of this treatment?

Prostate cancer treatments primarily target androgen signaling, which is crucial for prostate cancer cell growth. Androgen deprivation therapy (ADT) reduces testosterone levels, slowing cancer progression. Abiraterone inhibits androgen production, while enzalutamide blocks androgen receptors, both enhancing ADT's effectiveness. Docetaxel, a chemotherapy agent, disrupts cell division, particularly in rapidly growing cancer cells. Sipuleucel-T, an immunotherapy, stimulates the immune system to attack prostate cancer cells. Genomic testing is essential to identify actionable mutations, guiding personalized treatment strategies. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics.

Phase 1

Recruiting

Research Sponsored by Amgen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Total serum testosterone <= 50 ng/dL or 1.7 nmol/L.

Dose exploration phase: Novel antiandrogen therapy must have been given for treatment of metastatic disease.

Must not have

Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.

Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of investigational product administration.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up year 1, 2, and 3

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called AMG 509 in adults to see if it is safe and to find the best dose. The study will monitor how people react to different doses.

Who is the study for?

Men with advanced prostate cancer that has spread and is resistant to hormone therapy can join. They should have tried a new antiandrogen treatment for metastatic disease, but not more than two taxane chemotherapies. Participants must be on or have had hormonal suppression therapy, show signs of cancer progression, and have good blood counts and organ function.

What is being tested?

The trial tests AMG 509's safety and the highest dose patients can tolerate without severe side effects (MTD/RP2D). It also looks at how well it works in men who are about to start treatments like abiraterone or enzalutamide for the first time.

What are the potential side effects?

Possible side effects include reactions related to immune system activation, such as inflammation in different parts of the body, fatigue, changes in blood cell counts which could affect infection risk or cause anemia, liver enzyme alterations indicating liver stress, and potential heart issues.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My testosterone levels are low, at or below 50 ng/dL.

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I have been treated with a new antiandrogen therapy for my metastatic disease.

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I have never taken abiraterone acetate before.

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I have metastatic prostate cancer and have had limited hormone or chemotherapy.

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I have never taken enzalutamide or similar medications before.

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I have had surgery to remove both testicles or am on hormone therapy for cancer.

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I have mCRPC and have had at most one type of hormone therapy but never docetaxel.

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I am fully active or can carry out light work.

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My platelet count is healthy without recent transfusions.

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My kidney function, based on a specific test, is at a safe level for the trial.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have an autoimmune disease or need permanent immunosuppressive therapy.

Select...

I have not had signs of a serious infection in the last 7 days.

Select...

My prostate cancer is not adenocarcinoma but a different type.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ year 1, 2, and 3

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~year 1, 2, and 3

This trial's timeline: 3 weeks for screening, Varies for treatment, and year 1, 2, and 3 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

1, 2, and 3-year overall survival (OS)

1, 2, and 3-year radiographic PFS

6 month radiographic PFS

+19 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: Part 5: AMG 509 IV Monotherapy in Outpatient SettingExperimental Treatment1 Intervention

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 DLRT recommendations and will utilize the doses explored in Part 1 dose-expansion phase

Group II: Part 4: AMG 509 IV Combination TherapyExperimental Treatment3 Interventions

Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 0/2 prior NHT (for hormone sensitive or castration-resistant disease) at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A), or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 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. The dose-expansion phase will confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and correlative biomarker analysis.

Group III: Part 3: AMG 509 IV Monotherapy in Earlier Lines of TreatmentExperimental Treatment1 Intervention

Part 3 will explore AMG 509 in participants with mCRPC who have received 1 prior NHT (may have been given for HSPC) and no prior taxanes (may have been given for HSPC). 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.

Group IV: Part 2: AMG 509 Subcutaneous (SC) MonotherapyExperimental Treatment1 Intervention

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.

Group V: Part 1: AMG 509 Intravenous (IV) MonotherapyExperimental Treatment1 Intervention

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Abiraterone

2012

Completed Phase 4

~4480

Enzalutamide

2014

Completed Phase 4

~3820

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Prostate cancer treatments primarily target androgen signaling, which is crucial for prostate cancer cell growth. Androgen deprivation therapy (ADT) reduces testosterone levels, slowing cancer progression. Abiraterone inhibits androgen production, while enzalutamide blocks androgen receptors, both enhancing ADT's effectiveness. Docetaxel, a chemotherapy agent, disrupts cell division, particularly in rapidly growing cancer cells. Sipuleucel-T, an immunotherapy, stimulates the immune system to attack prostate cancer cells. Genomic testing is essential to identify actionable mutations, guiding personalized treatment strategies. Understanding these mechanisms helps patients and doctors choose the most effective treatment based on the cancer's specific characteristics.

Active surveillance for low-risk prostate cancer.