IRB Study Number 25-051
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
To compare overall survival (OS) in subjects receiving xaluritamig vs investigator’s choice (cabazitaxel or second androgen receptor-directed therapy [ARDT])
Secondary Objectives
To compare radiographic progression-free survival (rPFS) in subjects receiving xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
To evaluate other measures of efficacy of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
To compare symptomatic skeletal events (SSE) in subjects treated with xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
To evaluate the safety and tolerability of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
To evaluate health-related quality of life (HRQoL) of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
To evaluate patient-reported safety and tolerability of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
Evaluate the biochemical response of xaluritamig vs investigator’s choice (cabazitaxel or second ARDT)
Characterize the pharmacokinetics (PK) of xaluritamig using intensive and sparse PK sampling
Evaluate the immunogenicity of xaluritamig
Inclusion Criteria
101 Subject has provided informed consent(s) prior to initiation of any study specific activities/procedures.
102 Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years) at the time of signing the informed consent.
103 Subject must have histological, pathological and/or cytological confirmation of adenocarcinoma of the prostate.
104 mCRPC with ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging obtained within 28 days prior to enrollment.
105 Evidence of progressive disease, defined as 1 or more PCWG3 criteria:
Serum PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week prior. The minimal start value is 2.0 ng/mL. This must be assessed locally for eligibility (see Schedule of Activities Section 1.3).
Soft-tissue progression defined as an increase 20% in the sum of the diameter (SOD) (short axis for nodal lesions and long axis for non-nodal lesions) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions.
Progression of bone disease: evaluable disease or new bone lesions(s) by bone scan (2+2 PCWG3 criteria, Scher et al, 2016).
106 Subjects must have prior orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum testosterone (< 50 ng/dL or < 1.7 nmol/L). This must be assessed locally for eligibility (see Schedule of Activities Section 1.3).
107 Prior treatment with at least one ARDT.
108 Prior treatment with one taxane therapy. Prior treatment with docetaxel in the hormone-sensitive setting is permitted. Subjects who received two or more prior chemotherapy regimens in the castrate-resistant setting are not eligible.
109 Prior treatment with radioligand therapy (RLT), radionuclide therapy (Radium-223), poly adenosine diphosphate ribose polymerase (PARP) inhibitor, or immune checkpoint inhibitor is permitted.
110 Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1.
111 Adequate organ function, defined as follows: Hematological function:
− white blood cell count ≥ 2.5 x 109/L OR absolute neutrophil count ≥ 1.5 x 109/L.
− platelet count ≥ 75 x 109/L.
− hemoglobin ≥ 9 g/dl (90 g/L).
Renal function:
− estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation ≥ 30 ml/min/1.73 m2.
Hepatic function:
− AST and ALT ≤ 3 X upper limit of normal (ULN) (or ≤ 5 X ULN for subjects with liver involvement).
− total bilirubin (TBL) ≤ 1.5 X ULN (or ≤ 2 X ULN for subjects with liver involvement). For patients with known Gilbert’s Syndrome, < 3 X ULN is permitted.
Pulmonary function:
− Baseline oxygen saturation > 92% on room air at rest and no oxygen supplementation.
Cardiac function:
− left ventricular ejection fraction > 50% (screening echocardiography only required in subjects with known history of cardiac disease, prior MI, angina pectoris, coronary artery bypass graft [CABG], angioplasty, stent placement).
112 Life expectancy of ≥ 12 weeks per treating physician’s assessment.
Exclusion Criteria
Prior & Concomitant Therapy
201 Prior STEAP1-targeted therapy.
202 Any anticancer therapy, immunotherapy, or investigational agent within 4 weeks
prior to first dose of study treatment, not including androgen suppression therapy.
203 Prior PSMA RLT within 2 months of first dose of study treatment unless subjects received < 2 cycles of therapy. Subjects who received 1 cycle of PSMA RLT within 35 days prior to first dose of study treatment are also excluded. Prior radionuclide therapy (Radium-223) within 2 months of first dose of study treatment.
204 Subjects who started a bisphosphonate or denosumab regimen within 4 weeks prior to first dose of study treatment.
205 Radiation therapy within 4 weeks prior to first dose of study treatment (or local or focal radiotherapy within 2 weeks prior to first dose of study treatment).
206 Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological therapy, investigational therapy.
Disease Related
207 Patients with a history of central nervous system (CNS) metastasis.
208 Unresolved toxicities from prior anti-tumor therapy with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 events grade above 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.
Other Medical Conditions
209 History of malignancy that is expected to alter life expectancy or may interfere with disease assessments. Subjects 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.
210 History of allergic reactions or acute hypersensitivity reactions to the components of the study therapies and their analogs. (Patients with a known hypersensitivity to docetaxel and pursuing intention to treat with second ARDT are eligible).
211 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 hyper-thyroid disease not requiring immunosuppressive treatment are permitted.
212 History or evidence of inflammatory bowel disease (ulcerative colitis or Crohn disease) or any other gastrointestinal disorder causing chronic nausea, vomiting, or diarrhea (defined as CTCAE grade 2).
213 Evidence of interstitial lung disease or active, non-infectious pneumonitis, or uncontrolled asthma.
214 Recent history of arterial (eg, stroke or transient ischemic attack) or venous (eg, 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 (eg, 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.
215 Recent history of myocardial infarction 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 myocardial infarction controlled with stent placement and confirmed by a cardiologist more than 6 months prior to first dose of study treatment.
216 Known:
human immunodeficiency virus (HIV) infection (subjects 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 (subjects with hepatitis C that achieve a sustained virologic response after antiviral therapy are allowed),
hepatitis B infection (subjects 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).
217 Concurrent serious medical conditions, including, but not limited to, uncontrolled infection, other significant co-morbid conditions including somatic or psychiatric disease/condition that in the opinion of the investigator would impair study participation or cooperation.
218 History of solid organ transplant.
219 Major surgical procedures within 4 weeks prior to first dose of study treatment.
220 Transfusion dependent patients are allowed on the study, however, transfusion for the sole purpose of making a subject eligible for study inclusion is not allowed.
Prior/Concurrent Clinical Study Experience
221 Currently receiving treatment in another investigational device or drug study, or less than 30 days 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.
Other Exclusions
222 Male subjects who are unwilling to abstain from donating sperm during treatment and male subjects 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 4 months after last dose of cabazitaxel, an additional 3 months after last dose of enzalutamide, or an additional 3 weeks after last dose of abiraterone acetate. Refer to Section 11.5 for additional contraceptive information.
223 Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, Clinical Outcome Assessments) to the best of the subject and investigator’s knowledge.
224 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 subject safety, or interfere with the study evaluation, procedures, or completion.
