Study of AR Suppression With Carotuximab in Metastatic, Castration-Resistant Prostate Canc

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexMale
• Healthy volunteersNo

You may be able to join if

• History of castration-resistant prostate cancer with rising PSA on a contemporary ARSI (e.g. abiraterone or, enzalutamide, darolutamide). Bicalutamide, nilutamide, and flutamide will not be considered as contemporary ARSIs.
• PSA rise will be defined as an increase in PSA of 0.2 ng/mL or higher on at least 2 separate occasions greater than 1 week apart while on an ARSI
• Patient must be surgically castrated or have serum testosterone concentrations much be consistent with castrate levels of testosterone (under 50 ng/dL) while on LHRH analog therapy
• Patient must have had 1 and can have up to 2 prior AR targeted agents (if patients have had previous enzalutamide, they will be considered only for arm C). therapy with the exception of apalutamide.
• Patients may not have had previous chemotherapy with the exception of docetaxel administered for castration-sensitive disease.
• Patients must decline or be ineligible for taxane therapy in the opinion of the treating physician.
• Have Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1
• Resolution of adverse events results as described below:
• If the subject's patient's most recent line of therapy is treatment with abiraterone or enzalutamide, then all adverse events must be resolved to Grade 2 or less
• If the subject's patient's most recent line of therapy is any other treatment for mCRPC then all Adverse events must be resolved to grade 1 or less, with the exception of fatigue, alopecia and neuropathy (which must resolve to CTCAE grade 2)
• Adequate organ function
• All patients must agree to use an adequate method of contraception, in the opinion of the treating investigator, while on protocol treatment and for 3 months after the last dose of protocol treatment (apalutamide/enzalutamide and/or carotuximab)
• Written informed consent obtained from subject and ability for subject to comply with the requirements of the study

You cannot join if

• Non-PSA producing prostate cancers such as small cell prostate cancers or those prostate cancers which exhibit radiographic progression without PSA rise
• Other prior malignancy requiring active anticancer therapy
• Prior exposure to carotuximab or any CD105 targeted antibody
• Any major surgical procedure, in the opinion of the treating physician, within 2 weeks of starting therapy
• Uncontrolled chronic hypertension defined as sustained systolic pressure (SBP) >150 mmHg or diastolic pressure (DBP) >90 despite optimal therapy
• Active bleeding or pathologic medical conditions, including but not limited to factor deficiencies, hemophilia, etc., that carries a high bleeding risk
• Use of thrombolytics within 10 days prior to the first day of carotuximab
• Known hypersensitivity to Chinese hamster ovary products or other recombinant human, chimeric, or humanized antibodies
• A known diagnosis of Osler-Weber-Rendu syndrome
• Ascites or pericardial or pleural effusion requiring external drainage procedures
• History of untreated brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease. Patients with radiated or resected lesions are permitted, provided the lesions are fully treated and inactive, patients are asymptomatic, and no steroids have been administered for at least 28 days. Imaging for CNS disease will not be required for screening unless there is a history of a neurological finding such as new onset of weakness or numbness that cannot be explained by other medical history.
• Acute cardiovascular event within the past 6 months. An acute cardiovascular event will be defined as a myocardial infarction, NYHA Class II or worse congestive heart failure, cerebrovascular accident, transient ischemic attack, arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or CABG.
• Deep venous thrombosis within the past 6 months, unless the patient is anti-coagulated without the use of warfarin for at least 2 weeks. In this situation, low molecular weight heparin is preferred but clearance should be given by the local PI.

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

carotuximab. A human/murine chimeric monoclonal antibody directed against endoglin (CD105) with potential antiangiogenic and antineoplastic activities. Carotuximab binds to endoglin, which may result in inhibition of tumor angiogenesis and decreased tumor cell proliferation. The glycoprotein endoglin is a transforming growth factor beta-1 (TGF beta-1) accessory receptor that is highly expressed on tumor vessel endothelial cells and appears to be essential for angiogenesis. NCI Drug Dictionary

deuterated enzalutamide. A deuterated form of enzalutamide, an orally bioavailable, organic, non-steroidal small molecule targeting the androgen receptor (AR) with potential antineoplastic activity. Upon administration, deuterated enzalutamide competitively binds to and inhibits the activity of ARs expressed on prostate cancer cells, which impairs nuclear translocation and DNA binding, resulting in apoptosis of prostate cancer cells. This results in a reduction in prostate cancer cell growth. AR overexpression in prostate cancer represents a key mechanism associated with prostate cancer hormone resistance. Deuterium incorporation, by replacing the hydrogen atoms of the N-CH3 moiety with deuterium atoms, decreases enzalutamide's metabolism and allows for an increased pharmacokinetic profile, thereby enhancing its anti-tumor efficacy compared to non-deuterated enzalutamide. As the deuterated form can’t cross the blood-brain barrier (BBB), the deuterated form also reduces the unwanted brain-related side effects of enzalutamide and improves its safety profile. NCI Drug Dictionary

Treatments listed in the registry

• AR Blockade (Drug): Standard of care Apalutamide 240 mg / Enzalutamide 160mg administered orally and daily on Days 1-28 of every 28 day cycle
• Carotuximab (Drug): Carotuximab administered intravenously at the following doses: Cycle 1 Day 1: 3 mg/kg Cycle 1 Day 4: 7 mg/kg Cycle 1 Day 8: 10 mg/kg Cycle 1 Day 15: 10 mg/kg Cycle 1 Day 22: 10 mg/kg Cycle 2 Day 1: 15 mg/kg Cycle 2 Day 15: 15 mg/kg Cycle 3+ Day 1: 15 mg/kg After completion of cycle 2, dosing of carotuximab will continue at a q4 week schedule using the 15 mg/kg dose.

Randomized · Parallel · masking: None

Main goals

• Progression free survival (rPFS) between patients receiving AR blockade and AR blockade + carotuximab (From the start of study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.)

Other goals

• Incidence of Adverse events (grade 3 or higher) related to carotuximab and AR blockade
• Overall radiographic response rate (ORR) of the combination of AR blockade + carotuximab
• Proportion of patients resistant to AR blockade benefit from the addition of carotuximab
• Overall radiographic response rate (ORR) in the overall population
• To determine the radiographic progression free survival (rPFS) in the overall population
• To determine the biochemical PFS (by PCWG3) in the overall population

Planned enrollment: 116 (estimated).

• City of Hope, Duarte, California
• Cedars-Sinai Medical Center, Los Angeles, California
• Huntsman Cancer Institute and Hospital, Salt Lake City, Utah

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT05534646
• NCI Drug Dictionary: C74010
• NCI Drug Dictionary: C71744

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 4, 2026. Public record; not medical advice.