Xaluritamig for Prostate Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Amgen
Must not be taking: Cytotoxic chemotherapy, Immunotherapy
Disqualifiers: Metastatic disease, Autoimmune disease, others
No Placebo Group
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.
12345How 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.
14678Eligibility 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.
+4 more
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.
+7 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: XaluritamigExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Minnesota Medical Center FairviewMinneapolis, MN
University of North Carolina at Chapel HillChapel Hill, NC
Levine Cancer InstituteCharlotte, NC
University of Texas Southwestern Medical CenterDallas, 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.
Nomograms to predict outcomes after 177Lu-PSMA therapy in men with metastatic castration-resistant prostate cancer: an international, multicentre, retrospective study. [2021]Label="BACKGROUND">Lutetium-177 (177Lu) prostate-specific membrane antigen (177Lu-PSMA) is a novel targeted treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Predictors of outcomes after 177Lu-PSMA to enhance its clinical implementation are yet to be identified. We aimed to develop nomograms to predict outcomes after 177Lu-PSMA in patients with mCRPC.
Prognostic biomarkers in the use of radium-223 in patients with metastatic castration-resistent prostate cancer. [2023]Label="OBJECTIVES" NlmCategory="OBJECTIVE">This study aimed to establish basal biomarkers in patients with bone metastatic castration-resistant prostate cancer (mCRPC) treated with 223Ra to predict better overall survival (OS), and assess hematologic toxicity and treatment response.
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.
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).
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.
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]177Lu-PSMA-617 is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC). However, treatment resistance occurs frequently, and combination therapies may improve outcomes. We report the final safety and efficacy results of a phase I/II study combining 177Lu-PSMA-617 with idronoxil (NOX66), a radiosensitizer, and examine potential clinical, blood-based, and imaging biomarkers. Methods: Fifty-six men with progressive mCRPC previously treated with taxane chemotherapy and novel androgen signaling inhibitor (ASI) were enrolled. Patients received up to 6 doses of 177Lu-PSMA-617 (7.5 GBq) on day 1 in combination with a NOX66 suppository on days 1-10 of each 6-wk cycle. Cohort 1 (n = 8) received 400 mg of NOX66, cohort 2 (n = 24) received 800 mg, and cohort 3 (n = 24) received 1,200 mg. 68Ga-PSMA and 18F-FDG PET/CT were performed at study entry, and semiquantitative imaging analysis was undertaken. Blood samples were collected for analysis of blood-based biomarkers, including androgen receptor splice variant 7 expression. The primary outcomes were safety and tolerability; secondary outcomes included efficacy, pain scores, and xerostomia. Regression analyses were performed to explore the prognostic value of baseline clinical, blood-based, and imaging parameters. Results: Fifty-six of the 100 men screened were enrolled (56%), with a screening failure rate of 26% (26/100) for PET imaging criteria. All men had received prior treatment with ASI and docetaxel, and 95% (53/56) had received cabazitaxel. Ninety-six percent (54/56) of patients received at least 2 cycles of combination NOX66 and 177Lu-PSMA-617, and 46% (26/56) completed 6 cycles. Common adverse events were anemia, fatigue, and xerostomia. Anal irritation attributable to NOX66 occurred in 38%. Forty-eight of 56 had a reduction in prostate-specific antigen (PSA) level (86%; 95% CI, 74%-94%); 34 of 56 (61%; 95% CI, 47%-74%) had a PSA reduction of at least 50%. Median PSA progression-free survival was 7.5 mo (95% CI, 5.9-9 mo), and median overall survival was 19.7 mo (95% CI, 9.5-30 mo). A higher PSMA SUVmean correlated with treatment response, whereas a higher PSMA tumor volume and prior treatment with ASI for less than 12 mo were associated with worse overall survival. Conclusion: NOX66 with 177Lu-PSMA-617 is a safe and feasible strategy in men being treated with third-line therapy and beyond for mCRPC. PSMA SUVmean, PSMA-avid tumor volume, and duration of treatment with ASI were independently associated with outcome.
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).