LuX: Xaluritamig in Participants With Metastatic Castrate Resistant Prostate Cancer and Suboptimal Response to Lutetium 177 Vipivotide Tetraxetan

NCT07737925 | Not Yet Recruiting Phase 2 FDA Drug

• 2 other identifiers: iRISID-2025-1294JT 47440
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a phase 2a, open label, single arm, multi-site study of xaluritamig in mCRPC patients following treatment with ≥1 ARPI, taxane chemotherapy (if eligible) and stable or partial PSA response following 2 cycles of lutetium 177 vipivotide tetraxetan. Participants will continue treatment until clinical or radiographic progression of disease, withdrawal, or toxicity requiring discontinuation of therapy. All participants will be evaluated for overall response per RECIST v1.1,8 radiographic progression free survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) criteria, and PSA response. Approximately 30 participants will be enrolled. There is no data on response with alternative treatments following lutetium 177 vipivotide tetraxetan against which to benchmark the response rate. This phase 2a study will serve as an exploratory pilot to determine if a larger phase 2b study is warranted in this setting.

Conditions

Prostate Cancer; Metastatic Castrate Resistant Prostate Cancer

Keywords

Xaluritamig; AMG509; Lutetium 177 Vipivotide Tetraxetan; Sequential Targeting; PSMA; STEAP1; T-cell engager; mCRPC

Outcome Measures

Primary Outcomes (1)

• Proportion of Participants who achieve Partial or Complete Response or PSA90

  Proportion of participants with mCRPC treated with xaluritamig after lutetium-177 vipivotide tetraxetan who achieve either: (1) a confirmed Complete Response (CR) or Partial Response (PR) within 24 weeks by local investigator assessment per RECIST v1.1 in participants with baseline measurable disease, with confirmation ≥4 weeks after initial response; or (2) a confirmed PSA90 response, defined as a ≥90% decline from baseline PSA in participants with baseline PSA ≥2.0 ng/mL within 24 weeks, confirmed by a subsequent PSA assessment obtained ≥2 weeks later. RECIST v1.1 classifies tumor response as CR (disappearance of all target lesions), PR (≥30% decrease in tumor size), Stable Disease (SD), or Progressive Disease (PD; ≥20% increase in tumor size or new lesions). Higher response rates indicate greater treatment efficacy.

  Baseline to 24 weeks

Secondary Outcomes (6)

• Radiographic Progression-Free Survival (rPFS)

  Up to 2 years post-treatment

• Duration of response (DOR)

  From Baseline measurable disease until the first date that progressive disease is objectively documented, assesed up to 58 months.

• Time to Prostate-Specific Antigen (PSA) response (30%, 50%, 70%, and 90%)

  assessed up to 58 months

• Time to Prostate-Specific Antigen (PSA) Progression

  From start of study treatment until documented PSA progression, assessed up to 58 months

• Duration of PSA 50/90 response

  assessed up to 58 months

Study Arms (1)

Arm 1: Xaluritamig

EXPERIMENTAL

Participants with metastatic castration-resistant prostate cancer (mCRPC) will be randomized to receive Xaluritamig as an intravenous (IV) infusion.

Drug: Xaluritamig

Interventions

Xaluritamig DRUG

short-term IV infusion

Arm 1: Xaluritamig

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in this study, participants should complete all screening procedures and meet all of the following criteria (i.e., evaluations performed as part of routine care prior to informed consent can be used for screening and eligibility confirmation):
• Willing and able to provide, or have a legally authorized representative provide, written informed consent and privacy authorization for the release of personal health information. A signed informed consent must be obtained before screening procedures are performed.
• NOTE: Privacy authorization may be either included in the informed consent or obtained separately.
• years of age and above
• Histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate.
• Prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (\<50 ng/dL or \<1.7 nmol/L).
• Received ≥1 novel ARPI (e.g., enzalutamide, darolutamide, apalutamide and/or abiraterone).
• Eastern Cooperative Oncology Group (ECOG) status of 0-2 (Appendix A).
• Life expectancy of \>6 months.
• Previously treated with, declined treatment with, or are considered unsuitable/unwilling for taxane regimen per investigator discretion.
• Prior completion of 2 cycles of lutetium 177 vipivotide tetraxetan between 16 and 6 weeks prior to initiation of study treatment, with evidence of PSA response between 0-90% decrease from the pre- lutetium 177 vipivotide tetraxetan baseline, documented by a PSA measurement obtained within 4 weeks of second dose of lutetium 177 vipivotide tetraxetan.
• Participants must have either:
• baseline measurable disease per RECIST v1.1 at time of screening or
• baseline PSA ≥ 2 ng/mL at time of screening.
• Patients must have adequate organ function:

You may not qualify if:

• Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessments in the judgment of the site Principal Investigator (PI). Participants with prior history of malignancy that have been adequately treated and who have been disease-free for \> 3 years are eligible, as are subjects with adequately treated non-melanoma skin cancer or superficial bladder cancer.
• Requirement for chronic systemic corticosteroid therapy (prednisone dose \>10 mg per day or equivalent) or any other immunosuppressive therapies (including anti-TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing. Corticosteroid treatment for adverse event management as described in Section 6.1.10 is allowed.
• Previous PSMA-targeted radioligand therapy, aside from treatment with 2 cycles of lutetium 177 vipivotide tetraxetan, is not allowed.
• Prior PSMA radioligand therapy within 6 weeks of first dose of study treatment.
• Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, or investigational therapy.
• Untreated central nervous system metastases or leptomeningeal disease, symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression.
• Active systemic infection treated with IV antibiotics within 7 days prior to the first dose of study drugs.
• Active autoimmune disease that has required systemic treatment (except replacement therapy) within the past 2 years or any other diseases requiring immunosuppressive therapy while on study. Participants with Type I diabetes, vitiligo, psoriasis, hypo or hyperthyroid disease not requiring immunosuppressive treatment are permitted.
• History or evidence of inflammatory bowel disease (ulcerative colitis or Chron disease) or any other gastrointestinal disorder causing chronic nausea, vomiting or diarrhea (CTCAE ≥ grade 2).
• Evidence of interstitial lung disease or active, non-infectious pneumonitis, or uncontrolled asthma.
• Recent history of arterial (e.g. stroke or transient ischemic attack) or venous (e.g., pulmonary embolism or deep vein thrombosis) thrombosis; within 12 and 6 months prior to first dose of study treatment, respectively.
• Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as determined by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval by Fredericia prolongation \> 480 ms, electrolyte disturbances, etc), or patients with congenital long QT syndrome.
• Recent history of myocardial infarction and/or symptomatic congestive hear failure (New York Heart Association ≥ class II) within 12 months of first dose of study treatment, with the exception of ischemia or non ST segment elevation myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of study treatment.
• Unresolved toxicities from prior anti-tumor therapy not having resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or less, with the exception of alopecia, neuropathy, endocrinopathy, xerostomia, or toxicities that are stable and well-controlled.
• Known allergy to any of the compounds under investigation.

Sponsors & Collaborators

• Thomas Jefferson University: lead
• Prostate Cancer Clinical Trials Consortium: collaborator
• Amgen: collaborator

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Kevin K Zarrabi, MD, MS

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Site Public Contact

CONTACT

215-600-9151; ONCTrialNow@jefferson.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 30, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): October 1, 2030
• Study Completion (Estimated): October 1, 2031
• Last Updated: July 30, 2026

Record last verified: 2026-07