Xaluritamig for Prostate Cancer

Recruiting at 7 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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

The main objective of this study is to evaluate the safety and tolerability of xaluritamig monotherapy in adult participants with high-risk biochemical recurrent (BCR) nonmetastatic castration-sensitive prostate cancer (nmCSPC).

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.

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

Xaluritamig has shown promising results in treating advanced prostate cancer by targeting and killing cancer cells that express a specific protein (STEAP1). 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}

How is the drug Xaluritamig unique in treating prostate cancer?

Xaluritamig is unique because it is a novel immunotherapy that targets a specific protein (STEAP1) found in prostate cancer cells, helping the immune system's T-cells to attack and kill these cancer cells. It is administered intravenously and has shown promising results in early studies, particularly in patients with advanced prostate cancer. ^{1 4 6 7 8}

Research Team

MD

Principal Investigator

Amgen

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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 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]

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 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. 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

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

3. Spain pubmed.ncbi.nlm.nih.gov

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

4. 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]

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]