Xaluritamig for Prostate Cancer

Recruiting at 10 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Amgen

Must not be taking: Cytotoxic chemotherapy, Immunotherapy

Disqualifiers: Metastatic disease, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety of a new drug, xaluritamig (also known as AMG-509), for prostate cancer that has returned after initial treatment but hasn't spread. It includes patients who have undergone surgery or radiation and now experience a rise in PSA levels (a protein level monitored to track prostate cancer) within a year. Participants should have a PSA level of at least 0.2 if treated with surgery or 2.0 if treated with radiation, and a PET scan must confirm a specific type of prostate cancer. This trial does not include those whose prostate cancer has spread to other parts of the body. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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 certain hormonal therapies or immunosuppressive treatments, you may need to discuss this with the trial team.

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

Research shows that xaluritamig, a treatment for prostate cancer, is generally easy for patients to handle. In earlier studies, some patients experienced mild CRS, an immune reaction causing fever and tiredness, mostly during the first treatment cycle. These side effects were manageable. The available data did not consistently link any serious side effects to the treatment. This suggests that xaluritamig is generally safe for patients. However, monitoring each patient's response during clinical trials remains important, as reactions can vary. ^{1 2 3 4 5}

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

Xaluritamig is unique because it is administered as a short-term intravenous infusion, which is different from many standard prostate cancer treatments like hormone therapy or oral medications. Researchers are excited about Xaluritamig because it introduces a novel approach by potentially targeting cancer cells more directly and aggressively over a concise treatment period of just six 28-day cycles. This could mean a faster response and fewer side effects compared to traditional therapies that often require longer treatment durations.

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

Research has shown that xaluritamig, the treatment under study in this trial, may help treat certain types of prostate cancer. In early studies with people, almost half of the patients who received xaluritamig experienced stable disease, meaning their cancer did not worsen. Lab tests conducted before human trials also demonstrated that xaluritamig has strong effects against prostate cancer cells. This drug targets a protein called STEAP1, found on prostate cancer cells, and helps the body's immune system attack these cells. These findings suggest that xaluritamig could be effective for some patients with prostate cancer. ^{1 4 5 6 7}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with high-risk, biochemically recurrent prostate cancer that hasn't spread and is still sensitive to hormone therapy. Participants must have had prior surgery or radiation with curative intent, a PSA doubling time of 12 months or less, and certain minimum PSA levels depending on treatment received.

Inclusion Criteria

My prostate cancer has returned after surgery or radiation.

I've had a specific PET scan within the last 3 months.

My PSA level is above the required minimum after my primary prostate cancer treatment.

Exclusion Criteria

I have received immunotherapy or other biologic treatments for prostate cancer.

My PET scan shows PSMA-positive lesions but no signs of cancer spread on regular scans.

I have received specific treatments for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Xaluritamig is administered as a short-term intravenous (IV) infusion for a total of 6 cycles, with each cycle consisting of 28 days

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of treatment-related adverse events

Up to approximately 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Xaluritamig

Trial Overview

The study focuses on the safety and tolerability of a medication called Xaluritamig when used alone in patients. It's aimed at those whose prostate cancer has returned but not spread after initial treatments like surgery or radiation.

How Is the Trial Designed?

Group I: Xaluritamig Experimental Treatment 1 Intervention

Xaluritamig will be administered as a short-term intravenous (IV) infusion for a total of 6 cycles. One treatment cycle consists of 28 days.

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 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]

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 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]

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 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]

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.

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

3.

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 ...

4.

urotoday.com

urotoday.com/conference-highlights/esmo-2024/esmo-2024-prostate-cancer/154804-esmo-2024-xaluritamig-a-steap1-x-cd3-xmab-2-1-immune-therapy-in-patients-pts-with-metastatic-castration-resistant-prostate-cancer-mcrpc-initial-results-from-dose-expansion-cohorts-in-a-phase-1-study.html

ESMO 2024: Xaluritamig, a STEAP1 x CD3 XmAb 2+1 ...

Notably, 49.3% of patients treated with Xaluritamig achieved stable disease. Xaluritamig efficacy. The duration of response was encouraging; however, the data ...

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.

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 ...

7.

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.