Xaluritamig for Prostate Cancer

Recruiting at 9 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

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new treatment called xaluritamig for prostate cancer. Researchers administer xaluritamig before prostate removal surgery to assess patient tolerance to this sequence. This study targets individuals diagnosed with intermediate- or high-risk localized prostate cancer who are already planning surgery. Participants should not have received any prior treatment for their prostate cancer. As a Phase 1 trial, this research aims to understand how xaluritamig works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that xaluritamig is likely to be safe for humans?

Earlier studies have shown that xaluritamig is safe for humans. Research indicates it can cause mild side effects, such as a slight fever during the first treatment cycle, which are usually manageable. One study found that xaluritamig was well-tolerated and suggested it could be safely administered to patients with prostate cancer. While this offers some reassurance about its safety, it is important to remember that this trial remains in the early testing stages. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Xaluritamig is unique because it is administered before undergoing radical prostatectomy, potentially enhancing its effectiveness. Unlike traditional treatments for prostate cancer, which often include hormone therapy or radiation, Xaluritamig offers a novel approach by targeting the cancer cells at a different stage. Researchers are excited about Xaluritamig because it could offer a new mechanism of action, possibly improving surgical outcomes and reducing the recurrence of cancer. This innovative approach is what sets Xaluritamig apart from current treatment options.

What evidence suggests that xaluritamig might be an effective treatment for prostate cancer?

Research has shown that xaluritamig, which participants in this trial will receive, may effectively treat prostate cancer. Studies have found that it can lower PSA levels and shrink tumors more effectively than previous treatments. Xaluritamig targets a protein called STEAP1 on prostate cancer cells, aiding the immune system in attacking these cells. Early tests in both lab models and humans suggest this method can combat prostate cancer while keeping side effects manageable. Although more research is needed, these early results indicate that xaluritamig could be a promising option for prostate cancer treatment. ^{5 6 7 8 9}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

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 an autoimmune disease or need ongoing immune-suppressing drugs.

I have received treatment for my prostate cancer before.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Cohort B - Xaluritamig with an Oral GnRH Antagonist Experimental Treatment 2 Interventions

Xaluritamig will be administered prior to radical prostatectomy. Participants will also receive an oral GnRH antagonist continuously up to the time of planned radical prostatectomy.

Group II: Cohort A - 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

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 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]

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]

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]

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]

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]

Citations

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

1765O Interim results from a phase I study of AMG 509 ... 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37861461/

Xaluritamig, a STEAP1 × CD3 XmAb 2+1 Immune Therapy for ... Xaluritamig demonstrated encouraging responses (PSA and RECIST) compared with historical established treatments for patients with late-line ...

3. 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

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS5118

Trial in progress (XALute): Phase 3 study of xaluritamig vs ... In a first-in-human study, xaluritamig demonstrated encouraging efficacy and a manageable safety profile for patients with mCRPC refractory to ...

5. 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 ... Characterization of AMG 509 (xaluritamig) in preclinical models demonstrated its potent antitumor activity against STEAP1-expressing prostate tumor cells.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07140900

NCT07140900 | Study Evaluating the Safety, Tolerability, ... The main objective of the trial is to evaluate the safety and tolerability of xaluritamig in combination with darolutamide or abiraterone. Official Title. A ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37861452/

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 ...

8. 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 ... Xaluritamig, a novel STEAP1 × CD3 XmAb 2+1 immune therapy for metastatic castrationresistant prostate cancer, can be safely administered and shows.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.5_suppl.TPS435

A phase 1b, open-label, multicenter study of xaluritamig in ... Statistical analysis for safety will include all enrolled patients receiving at least one dose of xaluritamig. Enrollment began in September ...