IRB Study Number 25-1115
Status Recruiting
Phase Phase 1
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
Description
-To evaluate the safety and tolerability of xaluritamig in combination with darolutamide or abiraterone
-To evaluate the preliminary efficacy of xaluritamig in combination with darolutamide or abiraterone
-Evaluate the PK of darolutamide or abiraterone
-Characterize the pharmacokinetics (PK) of xaluritamig in combination with darolutamide or abiraterone
-Evaluate the immunogenicity of xaluritamig in combination with darolutamide or abiraterone
-Evaluate exploratory biomarkers including pharmacodynamic and potential patient selection biomarkers
-To evaluate health related quality of life (HRQoL) of xaluritamig in combination with darolutamide or abiraterone
Inclusion Criteria
Participants have provided informed consent before initiation of any study-specific activities/procedures.
Age >/= 18 years or >/= legal age within the country if it is older than 18 years at the time of signing the informed consent.
Participants must have histological, pathological, and/or cytological confirmation of adenocarcinoma of the prostate. Mixed histologies (eg, adenocarcinoma with neuroendocrine component) are not permitted.
Participants must have at the time of diagnosis:
De novo mHSPC, defined as metastatic disease with no prior diagnosis of localized prostate cancer AND started ADT (LHRH agonist/antagonist or orchiectomy) with or without ARPI (defined as abiraterone OR darolutamide) as SOC, first treatment with ADT should be no longer than 12 weeks before screening. Prior docetaxel treatment is not permitted.
Participants must have at the time of diagnosis:
High-volume metastatic disease defined as presence of visceral metastasis and/or ≥ 4 bone metastases with at least one outside of the vertebral column and pelvis
Documented metastatic disease either by a positive bone scan, or for soft tissue or visceral metastases, either by contrast enhanced abdominal/pelvic/chest computed tomography (CT) or magnetic resonance imaging (MRI) scan.
Exclusion Criteria
Prior history of central nervous system (CNS) metastases.
Unresolved toxicities from prior anti-tumor therapy (excluding those related to ongoing ADT and ARPI) not having resolved to CTCAE version 5.0 grade 1 or baseline, with the exception of alopecia or toxicities that are stable and well-controlled AND there is an agreement to allow inclusion by both the investigator and the sponsor.
History of malignancy that is expected to alter life expectancy or may interfere with disease assessments. Participants with prior history of malignancy that have been adequately treated and who have been disease-free for > 3 years are eligible, as are participants with adequately treated non-melanoma skin cancer or superficial bladder cancer.
Contraindications to the components of the study therapies and their analogs or known sensitivity to any components of investigational product to be administered during dosing or supportive agents (eg, dexamethasone, tocilizumab). Participants with known contraindications to high-dose corticosteroids are also excluded.
Autoimmune disease requiring systemic immunosuppression within the past 2 years
History or evidence of inflammatory bowel disease (Ulcerative colitis or Crohn’s disease) or any other gastrointestinal disorder causing chronic nausea, vomiting, or diarrhea (defined as CTCAE >/= grade 2).
Evidence of interstitial lung disease or active, noninfectious pneumonitis, or uncontrolled asthma.
Recent history of arterial (eg, stroke or transient ischemic attack), or venous (eg, pulmonary embolism or deep vein thrombosis) thrombosis, within 6 and 3 months prior to first dose of study treatment, respectively. Note: Participants with a history of venous thrombosis must be on stable anticoagulation.
Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as determined by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation > 480 ms, electrolyte disturbances, etc), or participants with congenital long QT syndrome.
Recent MI and/or symptomatic congestive heart 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 MI controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of study treatment.
Known:
-human immunodeficiency virus (HIV) infection (participants with HIV infection on antiviral therapy and undetectable viral load are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on study),
-hepatitis C infection (participants with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed),
-or hepatitis B infection (participants with hepatitis B surface antigen (HBsAg) or core antibody that achieve sustained virologic response with antiviral therapy are permitted with a requirement for regular monitoring for reactivation for the duration of treatment on the study).
Participant with symptoms and/or clinical signs and/or radiographic signs that indicate an acute and/or uncontrolled active or 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.
-Participants with simple urinary tract infections and uncomplicated bacterial pharyngitis that are responding to active treatment are permitted.
Participants receiving antiviral therapy who meet the aforementioned criteria are eligible only if their antiviral regimens do not pose significant drug-drug interactions with the study treatments.
Concurrent serious medical conditions, including, but not limited to, uncontrolled infection, uncontrolled hypertension, other significant co-morbid conditions including somatic or psychiatric disease/condition that in the opinion of the investigator would impair study participation or cooperation.
Major surgical procedures within 4 weeks prior to first dose of study treatment.
Port placement is not considered a major surgical procedure.
History of solid organ transplant.
Prior/Concomitant Therapy:
-Prior STEAP1-targeted therapy.
-Prior radioligand therapy (RLT), PARP inhibitor, cytotoxic chemotherapy, aminoglutethimide or ketoconazole for prostate cancer, or any prior systemic biologic therapy, including immunotherapy for prostate cancer
-Prior enzalutamide or apalutamide within 15 days prior to enrollment.
-Requirement for chronic systemic corticosteroid therapy (prednisone dose > 10 mg per day or local equivalent) or any other immunosuppressive therapies (including anti TNFα therapies) unless stopped (with adequate tapering) within 7 days prior to dosing.
-Prior radiotherapy (to the prostate and/or to all visible metastatic lesions in a metastasis-directed therapy approach); palliative radiation within 2 weeks prior to first dose of study treatment is allowed.
-Treatment with live and live‑attenuated vaccines within 4 weeks before the first dose of treatment.
Prior/Concurrent Clinical Study Experience:
-Currently receiving treatment in another investigational device or drug study, or less than 4 weeks since ending treatment in another investigational device or drug study(ies). This does not apply to other investigational procedures or participation in observational research studies.
Other Exclusions:
Participants who are unwilling to abstain from donating sperm during treatment and participants with a pregnant partner or partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 6 months after the last dose of xaluritamig, an additional 3 weeks after the last dose of abiraterone acetate, or 1 week after the last dose of darolutamide. Refer to protocol for additional contraceptive information.
Participant is likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, handheld device) to the best of the participant and investigator’s knowledge.
History or evidence of any other clinically significant disorder, condition, or disease (except for those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety, or interfere with the study evaluation, procedures or completion.
