AMG 509 for Prostate Cancer

Recruiting at 69 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Amgen

Must be taking: GnRH agonist/antagonist

Must not be taking: Immunosuppressants, Anticancer therapy

Disqualifiers: Small cell carcinoma, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

479 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AMG 509, for individuals with advanced prostate cancer that resists standard hormone therapy. The goal is to assess the safety and effectiveness of AMG 509 when used alone or with other treatments like abiraterone acetate or enzalutamide. The trial seeks participants with metastatic castration-resistant prostate cancer—cancer that has spread and does not respond to standard hormone therapy—who have already tried treatments such as abiraterone acetate, enzalutamide, and taxane chemotherapy. This trial may be suitable for those who have not found success with these treatments. As a Phase 1 trial, the research focuses on understanding how AMG 509 works in people, offering participants the chance to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had any anti-cancer therapy or immunotherapy within 4 weeks of starting the trial, except for certain hormone therapies. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that AMG 509 is being tested for safety in people with prostate cancer. Early results suggest that patients generally tolerate AMG 509 well. Some participants have experienced side effects, but these are usually mild to moderate.

For those considering the intravenous (IV) form of AMG 509, past findings indicate that the treatment is safe at certain doses. Similar results have been found for the subcutaneous (SC) form. Researchers are carefully studying both forms to find the best dose that balances safety and effectiveness.

When AMG 509 is used with other drugs like abiraterone acetate, studies have found the combination to be tolerable, meaning side effects can be managed.

The treatment remains in early testing phases, so researchers continue to collect safety information. However, existing data is promising and suggests that AMG 509 could be a potential option for those with prostate cancer, with safety being a key focus of ongoing research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard of care for metastatic castration-resistant prostate cancer (mCRPC), which typically involves hormone therapies and chemotherapy drugs, AMG 509 offers a new approach. Researchers are excited about AMG 509 because it targets prostate-specific membrane antigen (PSMA), a protein highly expressed in prostate cancer cells, providing a more precise attack on cancer cells. Additionally, AMG 509 is being explored both as an intravenous and subcutaneous treatment, offering flexibility that could improve patient convenience and comfort. This dual delivery method, along with its novel targeting mechanism, distinguishes AMG 509 from existing treatments and presents the potential for enhanced efficacy and tolerability.

What evidence suggests that AMG 509 could be an effective treatment for prostate cancer?

Research has shown that AMG 509 might help treat a type of prostate cancer that has spread and does not respond to hormone therapy. Early studies found that AMG 509 targets a protein called STEAP1, which often appears in large amounts on prostate cancer cells. By targeting this protein, AMG 509 helps the immune system identify and attack the cancer cells. Initial results suggest that AMG 509 can be effective, even for patients who have tried other treatments. This trial will evaluate AMG 509 in various treatment arms, including as monotherapy and in combination with abiraterone acetate, to further assess its efficacy and safety. While these findings are encouraging, more research is needed to confirm its effectiveness and safety. ^{1 2 4 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My heart is functioning well.

appearance of 2 or more new lesions in bone scan.

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

Exclusion Criteria

I have had brain metastases treated and they have not worsened since my last treatment.

I have an autoimmune disease or need permanent immunosuppressive therapy.

I have had a clot in my arteries or veins but it's been stable for the required time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Exploration

Evaluate AMG 509 in participants with mCRPC to estimate the maximum tolerated dose (MTD) using a Bayesian logistic regression model

12 weeks

Multiple visits for dose adjustments and monitoring

Dose Expansion

Confirm safety, tolerability, and pharmacokinetics of AMG 509 at the MTD or RP2D in different cohorts

12 weeks

Regular visits for safety and efficacy assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Periodic visits for long-term monitoring

What Are the Treatments Tested in This Trial?

Interventions

• AMG 509

Trial Overview 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.

How Is the Trial Designed?

Group I: Part 7 (China only): AMG 509 IV as Monotherapy or in Combination With Abiraterone Acetate Experimental Treatment 2 Interventions

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.

Group II: Part 6: AMG 509 IV as Monotherapy and Combination Therapy With Abiraterone Acetate Experimental Treatment 2 Interventions

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.

Group III: Part 5: AMG 509 IV Monotherapy in Outpatient Setting Experimental Treatment 1 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 dose level review team (DLRT) recommendations and will utilize the doses explored in Part 1 dose-expansion phase.

Group IV: Part 4: AMG 509 IV Combination Therapy Experimental Treatment 3 Interventions

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.

Group V: Part 3: AMG 509 IV Monotherapy in Earlier Lines of Treatment Experimental Treatment 1 Intervention

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.

Group VI: Part 2: AMG 509 Subcutaneous (SC) Monotherapy Experimental Treatment 1 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 VII: Part 1: AMG 509 Intravenous (IV) Monotherapy Experimental Treatment 1 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 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.

Who Is Running the Clinical Trial?

Amgen

Lead Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

BeOne (China only)

Collaborator

Published Research Related to This Trial

In the PREVAIL study involving 872 men with metastatic castration-resistant prostate cancer, significant declines in prostate-specific antigen (PSA) levels after 3 months of enzalutamide treatment were linked to improved overall survival and progression-free survival outcomes.

Specifically, 88% of patients experienced a PSA decline of at least 30%, and greater declines were associated with longer survival and better quality of life, indicating that monitoring PSA levels can provide valuable prognostic information for treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Association of Prostate-specific Antigen Decline with Clinical Outcomes in Men with Metastatic Castration-resistant Prostate Cancer Treated with Enzalutamide in a Randomized Clinical Trial. Armstrong, AJ., Lin, P., Higano, CS., et al.[2021]

In the AFFIRM trial involving 1199 men with metastatic castration-resistant prostate cancer, enzalutamide significantly improved overall survival (OS) and reduced prostate-specific antigen (PSA) levels compared to placebo, indicating its efficacy as a treatment after chemotherapy.

PSA declines of any amount, as well as declines of 30% and 50%, were strongly associated with better clinical outcomes, including improved OS and progression-free survival (PFS), suggesting that monitoring PSA levels can be important for assessing treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel. Armstrong, AJ., Saad, F., Phung, D., et al.[2022]

AMG 509 is a novel T-cell engager designed to target the STEAP1 antigen, which is commonly expressed in prostate tumors, particularly in metastatic castration-resistant prostate cancer (mCRPC), showing promising results in preclinical models by effectively killing cancer cells and promoting tumor regression.

In a clinical case study, a patient with mCRPC treated with AMG 509 achieved an objective response, highlighting its potential as a targeted immunotherapy for prostate cancer, especially in challenging cases where traditional treatments have limited success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer. Nolan-Stevaux, O., Li, C., Liang, L., et al.[2023]

In a study of 42 patients with nonmetastatic, castrate-resistant prostate cancer, those who received a poxvirus-based PSA vaccine showed a trend toward improved median survival (5.1 years) compared to those who received nilutamide (3.4 years).

Patients who initially received the vaccine and later switched to nilutamide had significantly better survival rates (6.2 years) compared to those who started with nilutamide and then received the vaccine (3.7 years), suggesting that the order of treatment may impact outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy. Madan, RA., Gulley, JL., Schlom, J., et al.[2021]

The combination of personalized peptide vaccination (PPV) and estramustine phosphate (EMP) was found to be safe for patients with castration-resistant prostate cancer (CRPC), with no serious treatment-related adverse events reported and only mild skin reactions observed.

The treatment successfully boosted immune responses in a significant portion of patients, with 67% showing enhanced cytotoxic T lymphocyte responses, and a median survival time of 23.8 months, suggesting promising antitumor activity that warrants further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of personalized peptide vaccination using 14 kinds of vaccine in combination with low-dose estramustine in HLA-A24-positive patients with castration-resistant prostate cancer. Noguchi, M., Uemura, H., Naito, S., et al.[2013]

The FDA approved Pluvicto (177Lu-PSMA-617) for treating metastatic castration-resistant prostate cancer (mCRPC) in patients who have undergone prior treatments, showing a significant improvement in overall survival (15.3 months vs. 11.3 months with standard care) in a trial with 831 participants.

Common side effects of Pluvicto include fatigue, dry mouth, and nausea, with notable laboratory abnormalities such as decreased lymphocytes and hemoglobin occurring in over 30% of patients, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. Fallah, J., Agrawal, S., Gittleman, H., et al.[2023]

Sipuleucel-T is the first FDA-approved autologous cellular immunotherapy for prostate cancer, designed to stimulate the immune system by using the patient's own cells to target a specific tumor-associated antigen, leading to a robust immune response.

In clinical studies, sipuleucel-T has shown a survival benefit for patients with metastatic castrate-resistant prostate cancer, with adverse events being mostly mild to moderate and comparable to those experienced by control subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of sipuleucel-T: autologous cellular immunotherapy for the treatment of metastatic castrate resistant prostate cancer. Sims, RB.[2016]

Xaluritamig (AMG 509) is a promising new immunotherapy targeting STEAP1 in patients with metastatic castration-resistant prostate cancer (mCRPC), showing encouraging efficacy with a 49% PSA response rate and a 24% objective response rate in a study of 97 patients.

The maximum tolerated dose was determined to be 1.5 mg administered weekly, with cytokine release syndrome being the most common side effect, occurring in 72% of patients but manageable with premedication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for Metastatic Castration-Resistant Prostate Cancer: Results from Dose Exploration in a First-in-Human Study. Kelly, WK., Danila, DC., Lin, CC., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04221542

NCT04221542 | Study of AMG 509 in Participants With ... A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534%2823%2903552-4/fulltext

1765O Interim results from a phase I study of AMG 509 ... A phase I study of AMG 509 (xaluritamig), a STEAP1 x CD3 XmAb 2+1 immune therapy, in patients with metastatic castration-resistant prostate cancer (mCRPC)

3. urotoday.com urotoday.com/video-lectures/esmo-2023/video/3686-amg-509-s-potential-in-prostate-cancer-therapy-michael-morris.html

AMG 509's Potential in Prostate Cancer Therapy - Michael ... This promising early-phase study, still determining optimal dosages, shows potential in treating prostate cancer, a field historically resistant ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.TPS5101

A phase 1 study of AMG 509 in patients (pts) with ... This 4-part, first-in-human study will evaluate AMG 509 in pts with mCRPC previously treated with novel hormonal therapy (NHT) and will assess the safety, ...

5. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/1/76/732544/Xaluritamig-a-STEAP1-CD3-XmAb-2-1-Immune-Therapy

Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for ... This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane ...

6. amgentrials.com amgentrials.com/study/?id=20180146

Study of AMG 509 in Participants with Metastatic Castration ... A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer.

7. aacrjournals.org aacrjournals.org/cancerdiscovery/article/14/1/90/732548/AMG-509-Xaluritamig-an-Anti-STEAP1-XmAb-2-1-T-cell

AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell ... AMG 509 mediates potent T cell–dependent cytotoxicity of prostate cancer cell lines in vitro and promotes tumor regression in xenograft and syngeneic mouse ...