Xaluritamig for Prostate Cancer

Recruiting at 6 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Antibiotics, Anticoagulants, Corticosteroids, others

Disqualifiers: Metastases, Autoimmune disease, Heart failure, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: Unknown

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on anticoagulation therapy, you may need to stop it temporarily for the surgery. It's best to discuss your specific medications with the trial team.

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

Xaluritamig has shown promising results in treating advanced prostate cancer by targeting a specific protein (STEAP1) found in most prostate tumors. In a study, 49% of patients experienced a significant reduction in prostate-specific antigen levels, and 24% had an objective response, indicating the drug's potential effectiveness. ^{1 2 3 4 5}

What makes the drug Xaluritamig unique for treating prostate cancer?

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. It is the first of its kind to advance to clinical testing, showing promising results in patients with advanced prostate cancer. ^{2 3 6 7 8}

What is the purpose of this trial?

The primary objectives of this study are to evaluate the safety and tolerability of xaluritamig administered in the neoadjuvant setting followed by radical prostatectomy and to evaluate the feasibility and safety of a radical prostatectomy following xaluritamig administered in the neoadjuvant setting.

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

Men with localized prostate cancer who are planning to have their prostate removed (radical prostatectomy) can join. They should be in good physical condition, with a Gleason score of at least 4+3 and/or advanced cancer visible on MRI or PSMA-PET scans. Participants must have had certain imaging tests within the last 3 months.

Inclusion Criteria

My prostate cancer is intermediate or high-risk with a Gleason score of 4+3 or higher, iPSA >10, or has spread to local lymph nodes.

I had a specific PET scan for prostate cancer within the last 3 months.

My prostate cancer was confirmed without certain aggressive features.

Exclusion Criteria

I have received treatment for my prostate cancer before.

My cancer has spread outside the surgery area, confirmed by scans.

I have an autoimmune disease or need ongoing immune-suppressing drugs.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Neoadjuvant Treatment

Participants receive xaluritamig prior to radical prostatectomy

6-8 weeks

Radical Prostatectomy

Participants undergo radical prostatectomy following neoadjuvant treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 months

Treatment Details

Interventions

• Xaluritamig

Trial Overview The trial is testing Xaluritamig given before surgery for prostate cancer. It aims to see how safe it is and if patients can still go through with the planned surgery after taking this drug.

Participant Groups

Group I: Xaluritamig Experimental Treatment 1 Intervention

Xaluritamig will be administered prior to radical prostatectomy.

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 a study involving 270 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with Lutetium-177 (177Lu-PSMA), nomograms were developed to predict overall survival and PSA-progression-free survival based on various clinical and imaging factors, achieving a C-index of 0.71 for overall survival.

The nomograms effectively stratified patients into low-risk and high-risk groups, with low-risk patients showing significantly longer overall survival (24.9 months) compared to high-risk patients (7.4 months), indicating their potential utility in clinical decision-making and trial design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. Gafita, A., Calais, J., Grogan, TR., et al.[2021]

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]

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 151 patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with 223Ra, those with higher hemoglobin levels (>13 g/dL), lower PSA (<20 ng/mL), and fewer bone metastases had significantly better overall survival, with a median survival of 34.9 months for those receiving complete treatment compared to 5.8 months for incomplete treatment.

The treatment was generally safe, with 70% of patients experiencing pain reduction and 66% showing decreased alkaline phosphatase levels, while only 5% experienced severe hematological adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistent prostate cancer. Vidal, M., Cárdenas-Perilla, R., Delgado, A., et al.[2023]

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]

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]

The combination of 177Lu-PSMA-617 and NOX66 is a safe and feasible treatment for men with metastatic castration-resistant prostate cancer (mCRPC), with 86% of patients showing a reduction in prostate-specific antigen (PSA) levels after treatment.

Patients experienced a median overall survival of 19.7 months, and factors like higher PSMA SUVmean were linked to better treatment responses, indicating potential biomarkers for predicting outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. Pathmanandavel, S., Crumbaker, M., Yam, AO., 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. [2021]

2. 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]

3. 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]

4. Spain pubmed.ncbi.nlm.nih.gov

Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistent prostate cancer. [2023]

5. 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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

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

177Lu-PSMA-617 and Idronoxil in Men with End-Stage Metastatic Castration-Resistant Prostate Cancer (LuPIN): Patient Outcomes and Predictors of Treatment Response in a Phase I/II Trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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