Evaluation of Neoadjuvant Xaluritamig in Localized Prostate Cancer

Official title

A Phase 1b, Open-Label, Multicenter Study Evaluating the Safety, Tolerability, and Feasibility of Neoadjuvant Xaluritamig Therapy Prior to Radical Prostatectomy in Subjects With Newly Diagnosed Localized Intermediate or High-Risk Prostate Cancer

Overview

The primary objectives of this study are to evaluate the safety and tolerability of xaluritamig administered as monotherapy or in combination with an oral Gonadotropin-releasing Hormone (GnRH) antagonist in the neoadjuvant setting followed by radical prostatectomy, and to evaluate the feasibility and safety of a radical prostatectomy following xaluritamig administered as monotherapy or in combination with an oral GnRH antagonist in the neoadjuvant setting.

Interventions

• Drug Xaluritamig
  Intravenous (IV) infusion
• Drug GnRH Antagonist
  Oral administration

Primary outcome measures

• Number of Participants who Experienced Treatment-emergent Adverse Events [Time frame: Up to 45 months]
• Number of Participants who Experienced Treatment-related Adverse Events [Time frame: Up to 28 months]
• Number of Participants who Received Radical Prostatectomy After Completing Xaluritamig Treatment [Time frame: Up to 25 months]
• Number of Participants who Experienced Complications of Radical Prostatectomy According to Clavien-Dindo Classification [Time frame: Up to 28 months]

Secondary outcome measures (12)

• Change in Prostate-specific Antigen (PSA) Levels from Baseline to End of Xaluritamig Treatment [Time frame: Up to 25 months]
• Prostate Imaging-Reporting and Data System (PI-RADS) Score [Time frame: Up to 25 months]
• Pathological Complete Response (pCR) Following Radical Prostatectomy [Time frame: Up to 25 months]
• Minimal Residual Disease (MRD) [Time frame: Up to 25 months]
• Number of Participants who Rise to PSA ≥ 0.2 ng/mL Post-radical Prostatectomy [Time frame: Up to 45 months]
• Time to PSA Rise ≥ 0.2 ng/mL Post-radical Prostatectomy [Time frame: Up to 45 months]
• Undetectable PSA at SFU [Time frame: Up to 26 months]
• PSA Progression-free Survival [Time frame: Up to 45 months]
• Maximum Serum Concentration (Cmax) of Xaluritamig [Time frame: Up to 45 months]
• Time to Maximum Concentration (Tmax) of Xaluritamig [Time frame: Up to 45 months]
• Area Under the Concentration Time Curve (AUC) Over the Dosing Interval [Time frame: Up to 45 months]
• Accumulation Following Multiple Dosing [Time frame: Up to 45 months]

Eligibility criteria

Inclusion criteria

Participants are eligible to be included in the study only if all the following criteria apply:

• Participants planned to undergo radical prostatectomy.
• Histologically or cytologically confirmed adenocarcinoma of the prostate at initial biopsy, without neuroendocrine differentiation, signet cell, or small cell features. Intermediate- or high-risk localized prostate cancer, defined as:

• Gleason score of 4+3 or higher AND initial PSA (iPSA) >10 OR
• Clinically advanced (cT3) on Magnetic Resonance Imaging (MRI) obtained within 3 months prior to screening AND/OR
• Positive locoregional lymph nodes as detected by prostate-specific membrane antigen-positron emission tomography (PSMA-PET) scans OR ≤ 5 local lymph nodes on MRI can be enrolled.
• Participants must have undergone a PSMA-PET (CT or MRI) scan within 3 months prior to screening as part of the standard of care (SOC).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

Exclusion criteria

Participants are excluded from the study if any of the following criteria apply:

• Prior treatment for participant's prostate cancer.

\- Exception: Participants intended for enrollment in cohort B may have received an oral GnRH antagonist up to 3 months prior to the start of screening.

• Any evidence of metastases outside of the surgical resection field identified by conventional imaging or PSMA-PET scans.
• Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy.
• Participants with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active systemic infection within 7 days prior to the first dose of study treatment:

\- Participant has known active infection requiring antibiotic treatment. Upon completion of antibiotics and resolution of symptoms, the participant may be considered eligible for the study from an infection standpoint.

• Recent history of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis) within 6 and 3 months prior to the first dose of study treatment, respectively. Note: Participants with a history of venous thrombosis must be on stable anti-coagulation.
• Myocardial infarction and/or symptomatic congestive heart failure (New York Heart Association ≥ class II) within 12 months of first dose of xaluritamig with the exception of ischemia or non-ST segment elevation myocardial infarction controlled with stent placement more than 6 months prior to first dose of xaluritamig.
• Requirement for chronic systemic corticosteroid therapy unless stopped (with adequate tapering) within 7 days prior to dosing.
• Currently receiving treatment in another investigational device or drug study, or less than 4 weeks (since ending treatment on another investigational device or drug study\[ies\]). Other investigational procedures and participation in observational research studies while participating in this study are excluded with the exception of investigational scans.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 7 centers

• University of California San Francisco — San Francisco
• Washington University — St Louis
• The Ohio State University — Columbus
• Thomas Jefferson University — Philadelphia
• Carolina Urologic Research Center — Myrtle Beach
• Fred Hutchinson Cancer Center — Seattle
• Medical College of Wisconsin — Milwaukee

Germany · 2 centers

• Universitaetsklinikum Essen — Essen
• Universitaetsklinikum Hamburg Eppendorf — Hamburg

Identifiers

NCT: NCT06613100 · 20230237 · 2024-511965-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗