Xaluritamig vs Other Treatments for Prostate Cancer

Recruiting at 203 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 3

Sponsor: Amgen

Must be taking: Androgen deprivation

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: CNS metastasis, Unresolved toxicities, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

675 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new drug, xaluritamig, extends the lives of people with advanced prostate cancer compared to other treatments. It will compare xaluritamig to cabazitaxel, a chemotherapy, or other hormone therapies targeting cancer growth. Men with prostate cancer that has spread and progressed despite previous treatments might be suitable candidates. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does require that you have not had any anticancer therapy, immunotherapy, or investigational agent within 4 weeks before starting the study treatment, except for ongoing androgen suppression therapy.

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

Research has shown that xaluritamig is generally safe for people with prostate cancer. In earlier studies, most patients who took xaluritamig experienced only mild side effects. A common issue was mild cytokine release syndrome (CRS), which usually occurred during the first treatment cycle. CRS can cause symptoms like fever or tiredness, but it was not severe for most participants.

Overall, xaluritamig has shown promise because patients, even those who had tried many other treatments, tolerated it well. This suggests that the drug is safe for further study in treating prostate cancer. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for prostate cancer?

Researchers are excited about Xaluritamig for prostate cancer because it offers a fresh approach by targeting metastatic castration-resistant prostate cancer (mCRPC) with a novel mechanism of action. Unlike standard treatments like cabazitaxel, abiraterone, and enzalutamide, which focus on hormone pathways or chemotherapy, Xaluritamig is designed to be administered as an intravenous infusion, potentially allowing for more direct and controlled delivery of the therapeutic agent. This innovative approach could provide new hope for patients who have limited options with existing treatments.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

In this trial, participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive either Xaluritamig or other treatments. Studies have shown that Xaluritamig, a new treatment that aids the immune system, has promising results for advanced prostate cancer unresponsive to hormone therapy. It targets a specific protein called STEAP1 on prostate cancer cells and activates the immune system to attack these cells. In early studies, patients who had tried several other treatments showed encouraging responses to Xaluritamig. The side effects were generally manageable, indicating they were not too severe for most patients. Overall, these findings suggest that Xaluritamig could be an effective option for this type of prostate cancer. ^{1 2 3 5 6}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with advanced prostate cancer that has spread and resisted treatment despite hormone therapy. They must have a confirmed diagnosis, show signs of progression on scans or rising PSA levels, and have previously received specific prostate cancer treatments but not more than one chemotherapy regimen in the castrate-resistant setting.

Inclusion Criteria

My cancer has grown by 20% or I have new cancer spots since starting treatment.

I have given my consent for all study-related procedures.

My PSA levels have increased twice after an initial reading of at least 2.0 ng/mL.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Xaluritamig as an IV infusion or investigator's choice of cabazitaxel, abiraterone, or enzalutamide

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Xaluritamig

Trial Overview

The study aims to compare overall survival between patients taking Xaluritamig and those receiving either Cabazitaxel or a second ARDT (like Abiraterone or Enzalutamide). It's designed to see if Xaluritamig can be more effective in treating this stage of prostate cancer.

How Is the Trial Designed?

Group I: Xaluritamig Experimental Treatment 1 Intervention

Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.

Group II: Cabazitaxel/Abiraterone/Enzalutamide Active Control 3 Interventions

Participants with mCRPC will be randomized to receive cabazitaxel as an IV infusion, or a second androgen receptor-directed therapy of either abiraterone as oral tablets, or enzalutamide as oral tablets at the investigator's discretion.

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

Published Research Related to This Trial

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 phase Ib study involving 45 men with metastatic castration-resistant prostate cancer (mCRPC), the combination of atezolizumab and radium-223 resulted in significant toxicity, with 52.3% of participants experiencing grade 3/4 adverse events, primarily related to atezolizumab.

The treatment showed a low confirmed objective response rate of only 6.8% and a median overall survival of 16.3 months, indicating that while the combination was safe to assess, it did not provide clear additional clinical benefits compared to the individual therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. Fong, L., Morris, MJ., Sartor, O., et al.[2023]

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]

Active surveillance is a promising approach for men with low-risk prostate cancer, helping to avoid unnecessary treatments and biopsies as more cancers are diagnosed early due to improved diagnostic methods.

For metastatic castration-resistant prostate cancer (mCRPC), newer therapies like abiraterone, enzalutamide, and docetaxel are now first-line treatments, showing significant survival benefits, while ongoing research is exploring combinations of these therapies with novel immunotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer-A Comprehensive Review. Malinowski, B., Wiciński, M., Musiała, N., et al.[2020]

In the phase 3 SPARTAN study involving 1207 patients with nonmetastatic castration-resistant prostate cancer, apalutamide significantly improved overall survival (OS) compared to placebo, with a median OS of 73.9 months versus 59.9 months, representing a 22% reduction in the hazard of death.

Apalutamide also delayed the need for cytotoxic chemotherapy, with a hazard ratio of 0.63, indicating a substantial benefit in managing disease progression compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Apalutamide and Overall Survival in Prostate Cancer. Smith, MR., Saad, F., Chowdhury, S., et al.[2022]

Sipuleucel-T is the first FDA-approved autologous active cellular immunotherapy for prostate cancer, designed to stimulate the immune system by using a patient's own cells to target a specific tumor-associated antigen, leading to improved survival in patients with metastatic castrate-resistant prostate cancer.

The treatment involves three infusions over approximately six weeks, with most adverse events being mild to moderate and resolving quickly, indicating a favorable safety profile for this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An overview of sipuleucel-T: autologous cellular immunotherapy for prostate cancer. Wesley, JD., Whitmore, J., Trager, J., et al.[2016]

In a Phase III trial involving 264 patients with advanced prostate cancer, the combination therapy of zoladex and flutamide showed only a small improvement in objective response compared to bilateral orchiectomy, but no significant differences in subjective response, time to progression, or overall survival.

Patients receiving the pharmacological treatment experienced more adverse effects, leading to the conclusion that the combination therapy is not clinically superior to orchiectomy for treating advanced prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate. Iversen, P., Christensen, MG., Friis, E., et al.[2019]

Prostate cancer is a significant health issue in men, accounting for one-third of all new cancer diagnoses in the USA, with 192,280 cases and 27,360 deaths reported in 2009.

There is a pressing need for new treatment options for metastatic castration-resistant prostate cancer, especially since traditional therapies have been limited after patients progress on docetaxel-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives. Lassi, K., Dawson, NA.[2011]

The KEYNOTE-641 study is a Phase III clinical trial designed to evaluate the safety and efficacy of combining the PD-1 inhibitor pembrolizumab with enzalutamide in men with metastatic castration-resistant prostate cancer (mCRPC).

This trial aims to determine if the combination therapy can improve outcomes compared to enzalutamide alone, addressing the need for more effective treatments in a patient population with a median survival of about 3 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. Graff, JN., Liang, LW., Kim, J., et al.[2021]

In a study of men with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T, a delayed PSA response was observed, with 19.9% of patients in the PROCEED registry showing a PSA50 response at a median of 5.5 months after treatment.

The median overall survival for patients in the PROCEED cohort was 49 months, suggesting that sipuleucel-T may provide a significant survival benefit despite low immediate response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in men with metastatic castration-resistant prostate cancer who received sipuleucel-T and no immediate subsequent therapy: experience at Dana Farber and in the PROCEED Registry. Wei, XX., Kwak, L., Hamid, A., et al.[2022]

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]

In a study of 32 men with bone-predominant metastatic castration-resistant prostate cancer, the combination of radium-223 and sipuleucel-T led to a significant increase in progression-free survival (39 weeks vs. 12 weeks) and overall survival (not reached vs. 2.6 years) compared to sipuleucel-T alone.

Despite the combination treatment showing lower immune responses (3.2-fold less T-cell response), it resulted in a higher rate of PSA decline (>50% in 31% of patients), suggesting that radium-223 may enhance the clinical effectiveness of sipuleucel-T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. Marshall, CH., Fu, W., Wang, H., et al.[2022]

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As of 23 March 2023, 97 pts in 15 DLs received ≥1 dose of xaluritamig. Median (range) age was 67 (40–86) years; 67 pts (69.1%) had received > 3 prior lines of ...

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