AMG 509 for Prostate Cancer

Recruiting at60 trial locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug AMG 509 for prostate cancer?

AMG 509, also known as Xaluritamig, has shown promising results in early studies for advanced prostate cancer. In a study, 49% of patients experienced a significant drop in prostate-specific antigen (PSA) levels, and 24% had an objective response, indicating the drug's potential effectiveness in treating this type of cancer. ^{1 2 3 4 5}

What makes the drug AMG 509 unique for prostate cancer treatment?

AMG 509 (Xaluritamig) is unique because it is a novel immunotherapy that targets a specific protein (STEAP1) found in most prostate tumors, redirecting T cells to attack cancer cells. This approach is different from traditional treatments as it specifically engages the immune system to fight cancer, showing promising results in early studies. ^{1 2 6 7 8}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• AMG 509 (Protein Kinase Inhibitor)

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.

Participant Groups

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

Group II: 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 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 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 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 IV: 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 V: 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 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.

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

Findings from Research

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]

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]

References

1. United States 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. [2023]

2. United States 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. [2023]

3. Netherlands 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. [2021]

4. United States 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Analysis of overall survival in patients with nonmetastatic castration-resistant prostate cancer treated with vaccine, nilutamide, and combination therapy. [2021]

6. United States 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. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

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