Xaluritamig vs Other Treatments for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+20 other locations
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.
12345What 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.
13678How 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.
19101112Eligibility 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
I have undergone treatment to lower my testosterone due to prostate cancer.
My prostate cancer has been confirmed by a lab test.
I have been treated with at least one androgen receptor-directed therapy.
My bone disease has worsened or new bone lesions have been found.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Active Control
Group I: XaluritamigExperimental Treatment1 Intervention
Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.
Group II: Cabazitaxel/Abiraterone/EnzalutamideActive Control3 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.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
University of California IrvineIrvine, CA
AdventHealth OrlandoOrlando, FL
Indiana UniversityIndianapolis, IN
University of Texas MD Anderson Cancer CenterHouston, TX
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Who is running the clinical trial?
AmgenLead Sponsor
References
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]Xaluritamig (AMG 509) is a six-transmembrane epithelial antigen of the prostate 1 (STEAP1)-targeted T-cell engager designed to facilitate lysis of STEAP1-expressing cancer cells, such as those in advanced prostate cancer. This first-in-human study reports monotherapy dose exploration for patients with metastatic castration-resistant prostate cancer (mCRPC), primarily taxane pretreated. Ninety-seven patients received ≥1 intravenous dose ranging from 0.001 to 2.0 mg weekly or every 2 weeks. MTD was identified as 1.5 mg i.v. weekly via a 3-step dose. The most common treatment-related adverse events were cytokine release syndrome (CRS; 72%), fatigue (45%), and myalgia (34%). CRS occurred primarily during cycle 1 and improved with premedication and step dosing. Prostate-specific antigen (PSA) and RECIST responses across cohorts were encouraging [49% PSA50; 24% objective response rate (ORR)], with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Xaluritamig is a novel immunotherapy for prostate cancer that has shown encouraging results supporting further development.
Drug development for metastatic castration-resistant prostate cancer: current status and future perspectives. [2011]Prostate cancer represents a third of all newly diagnosed cancers in men in the USA with an estimated incidence of 192,280 cases and 27,360 deaths in 2009. It continues to be a major cause of cancer-related morbidity and mortality, and there is an urgent need for new treatments. Historically, systemic therapy options were limited after progression on docetaxel-based chemotherapy. This article reviews current data on the novel therapeutics demonstrating activity in metastatic castration-resistant prostate cancer and their future role in the treatment of this disease with a poor prognosis.
Randomized Phase II Trial of Sipuleucel-T with or without Radium-223 in Men with Bone-metastatic Castration-resistant Prostate Cancer. [2022]To investigate whether radium-223 increases peripheral immune responses to sipuleucel-T in men with bone-predominant, minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).
Previous, Current, and Future Pharmacotherapy and Diagnosis of Prostate Cancer-A Comprehensive Review. [2020]Prostate cancer (PCa) is one of the most common cancers in men that usually develops slowly. Since diagnostic methods improved in the last decade and are highly precise, more cancers are diagnosed at an early stage. Active surveillance or watchful waiting are appealing approaches for men diagnosed with low-risk prostate cancer, and they are an antidote to the overtreatment problem and unnecessary biopsies. However, treatment depends on individual circumstances of a patient. Older hormonal therapies based on first generation antiandrogens and steroids were widely used in metastatic castration-resistant prostate cancer (mCRPC) patients prior to the implementation of docetaxel. Nowadays, accordingly to randomized clinical trials, abiraterone, enzalutamide, apalutamide. and docetaxel became first line agents administrated in the treatment of mCRPC. Furthermore, radium-223 is an optional therapy for bone-only metastasis patients. Sipuleucel-T demonstrated an overall survival benefit. However, other novel immunotherapeutics showed limitations in monotherapy. Possible combinations of new vaccines or immune checkpoint blockers with enzalutamide, abiraterone, radium-223, or docetaxel are the subject of ongoing rivalry regarding optimal therapy of prostate cancer.
Apalutamide and Overall Survival in Prostate Cancer. [2022]The phase 3 SPARTAN study evaluated apalutamide versus placebo in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and prostate-specific antigen doubling time of ≤10 mo. At primary analysis, apalutamide improved median metastasis-free survival (MFS) by 2 yr and overall survival (OS) data were immature.
KEYNOTE-641: a Phase III study of pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer. [2021]Current treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) are noncurative, and median survival upon development of mCRPC is approximately 3 years. The novel hormonal agent enzalutamide has an established role in the mCRPC treatment paradigm, and emerging evidence suggests potential synergism with enzalutamide and the PD-1 inhibitor pembrolizumab in men with mCRPC. Here, we describe the design and rationale for the multicenter, randomized, double-blind, Phase III KEYNOTE-641 study, which will be conducted to compare the efficacy and safety of pembrolizumab plus enzalutamide with that of enzalutamide plus placebo in mCRPC. Clinical trial registration: NCT03834493 (ClinicalTrials.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]Sipuleucel-T has demonstrated survival benefit in phase 3 trials but is utilized in few men with metastatic castration-resistant prostate cancer (mCRPC) in part due to low rates of PSA and objective response. Given the requirement to develop immune-mediated antitumor activity as vaccine-based therapy, sipuleucel-T may have delayed clinical activity. We explored this in a cohort of men from PROCEED (NCT01306890), an FDA-requested outcomes registry, and in a separate institutional cohort of mCRPC patients treated with sipuleucel-T at Dana-Farber Cancer Institute (DFCI).
A Phase Ib Study of Atezolizumab with Radium-223 Dichloride in Men with Metastatic Castration-Resistant Prostate Cancer. [2023]Men with metastatic castration-resistant prostate cancer (mCRPC) have limited treatment options after progressing on hormonal therapy and chemotherapy. Here, we evaluate the safety and efficacy of atezolizumab (anti-PD-L1) + radium-223 dichloride (radium-223) in men with mCRPC.
Development of sipuleucel-T: autologous cellular immunotherapy for the treatment of metastatic castrate resistant prostate cancer. [2016]Sipuleucel-T, the first autologous cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells, including autologous antigen presenting cells (APCs), with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase [PAP]) and granulocyte colony-macrophage stimulating factor (GM-CSF). A full course of treatment comprises 3 infusions of sipuleucel-T, given at approximately 2-week intervals. The pattern of APC activation is consistent with priming by the first infusion, and boosting by the second and third infusions. Preclinical and clinical studies have demonstrated evidence of a robust antigen-specific immune response that includes a progressive and persistent increase in antigen-specific cellular and humoral immune responses. Treatment with sipuleucel-T has demonstrated a survival benefit in Phase 3 studies of subjects with metastatic castrate resistant (hormone refractory) prostate cancer (mCRPC). Adverse events with sipuleucel-T were generally mild to moderate and resolved within 2 days. Serious adverse events, autoimmune events, and cerebrovascular events occurred at a similar rate to control subjects. As the first autologous cellular immunotherapy to demonstrate an improvement in overall survival in asymptomatic or minimally symptomatic mCRPC patients, sipuleucel-T represents a new treatment paradigm in oncology.
An overview of sipuleucel-T: autologous cellular immunotherapy for prostate cancer. [2016]Sipuleucel-T, the first autologous active cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells (including antigen presenting cells) with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase) and granulocyte-macrophage colony stimulating factor. Treatment consists of 3 infusions at approximately 2-week intervals, resulting in a prime-boost pattern of immune activation, a robust antigen-specific cellular and humoral immune response, and, consequently, a survival benefit in subjects with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer. Adverse events are generally mild to moderate and resolve within 2 d. Serious adverse events occur at a low rate. As the first autologous cellular immunotherapy to demonstrate a survival benefit, sipuleucel-T is a novel oncologic therapeutic that warrants the reassessment of the current prostate cancer treatment paradigm.
AMG 509 (Xaluritamig), an Anti-STEAP1 XmAb 2+1 T-cell Redirecting Immune Therapy with Avidity-Dependent Activity Against Prostate Cancer. [2023]The tumor-associated antigen Six-Transmembrane Epithelial Antigen of the Prostate 1 (STEAP1) is a potential therapeutic target that is expressed in most prostate tumors and at increased levels in metastatic castration-resistant prostate cancer (mCRPC). We developed a STEAP1-targeted XmAb 2+1 T-cell engager (TCE) molecule, AMG 509 (also designated xaluritamig), that is designed to redirect T cells to kill prostate cancer (PCa) cells that express STEAP1. AMG 509 mediates potent T cell-dependent cytotoxicity of PCa cell lines in vitro, and promotes tumor regression in xenograft and syngeneic mouse models of PCa in vivo. The avidity-driven activity of AMG 509 enables selectivity for tumor cells with high STEAP1 expression compared with normal cells. AMG 509 is the first STEAP1 TCE to advance to clinical testing, and we report a case study of a mCRPC patient who achieved an objective response on AMG 509 treatment.
A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate. [2019]In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate.