Xaluritamig vs Other Treatments for Prostate Cancer

Recruiting at 33 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Amgen

Must be taking: Androgen deprivation

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: CNS metastasis, Unresolved toxicities, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The main objective of the study is to compare overall survival in participants receiving xaluritamig versus investigator's choice (cabazitaxel or second androgen receptor-directed therapy \[ARDT\]).

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.

What data supports the effectiveness of the drug Xaluritamig for prostate cancer?

In a study with 97 patients having advanced prostate cancer, Xaluritamig showed promising results, with 49% of patients experiencing a significant drop in prostate-specific antigen levels and 24% showing an objective response to the treatment. These results were even better at higher doses, suggesting the drug's potential effectiveness. ^{1 2 3 4 5}

What safety data is available for Xaluritamig (AMG-509) in humans?

In a study with 97 patients, the most common side effects of Xaluritamig were cytokine release syndrome (a reaction that can cause fever and low blood pressure) in 72% of patients, fatigue in 45%, and muscle pain in 34%. These side effects were mostly seen during the first treatment cycle and improved with premedication and adjusted dosing. ^{1 3 6 7 8}

How is the drug Xaluritamig different from other treatments for prostate cancer?

Xaluritamig is unique because it is an immune therapy that targets a specific protein (STEAP1) found in prostate cancer cells, helping the body's T-cells to attack and kill these cancer cells. This approach is different from traditional treatments as it specifically engages the immune system to fight the cancer. ^{1 9 10 11 12}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Xaluritamig (Other)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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]

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 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]

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. England pubmed.ncbi.nlm.nih.gov

Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives. [2011]

3. United States 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. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer-A Comprehensive Review. [2020]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Apalutamide and Overall Survival in Prostate Cancer. [2022]

6. England pubmed.ncbi.nlm.nih.gov

KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. [2021]

7. England 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. [2022]

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

A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

An overview of sipuleucel-T: autologous cellular immunotherapy for prostate cancer. [2016]

11. 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]

12. United States 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. [2019]