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

NCT05534646 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IIT2021-06-Posadas-AR105
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 3

Brief Summary

This is an open-label, multi-site study of AR Blockade with carotuximab in patients who have progressed on androgen receptor signaling inhibitor (ARSI) therapy. This study will begin with a safety assessment in the first 10 subjects (part 1: Safety Lead-in). If the combination is deemed safe, the trial will proceed to the Phase II stage. The purpose of this study is to compare progression free survival (PFS) between patients receiving AR Blockade and AR Blockade + carotuximab using Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3. The secondary objectives are to describe adverse events related to the intervention, overall response rate (ORR), proportion of patients resistant to AR blockade that benefit from the addition of carotuximab, and to determine the ORR, radiographic PFS, and biochemical PFS in the overall population.

Conditions

Castration-resistant Prostate Cancer

Keywords

Prostate cancer; Castration-resistant; CRPC

Outcome Measures

Primary Outcomes (1)

• Progression free survival (rPFS) between patients receiving AR blockade and AR blockade + carotuximab

  From the start of study treatment until documented progression, per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3, or death due to any cause.

  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.

Secondary Outcomes (6)

• Incidence of Adverse events (grade 3 or higher) related to carotuximab and AR blockade

  From start of study treatment through 4 weeks on treatment

• Overall radiographic response rate (ORR) of the combination of AR blockade + carotuximab

  From the start of combination study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.

• Proportion of patients resistant to AR blockade benefit from the addition of carotuximab

  From the start of combination therapy study treatment until documented progression, or death due to any cause, up to 30 days of follow-up after end of treatment.

• Overall radiographic response rate (ORR) in the overall population

  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.

• To determine the radiographic progression free survival (rPFS) in the overall population

  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.

Study Arms (3)

Enzalutamide Naive - Monotherapy

ACTIVE COMPARATOR

After progression, subjects will crossover to combination therapy

Drug: AR Blockade

Enzalutamide Naive - Combination therapy (AR Blockade + Carotuximab)

EXPERIMENTAL

Drug: AR Blockade; Drug: Carotuximab

Enzalutamide Exposed - Combination therapy (AR Blockade + Carotuximab)

EXPERIMENTAL

Drug: AR Blockade; Drug: Carotuximab

Interventions

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.

Enzalutamide Exposed - Combination therapy (AR Blockade + Carotuximab); Enzalutamide Naive - Combination therapy (AR Blockade + Carotuximab)

AR Blockade DRUG

Standard of care Apalutamide 240 mg / Enzalutamide 160mg administered orally and daily on Days 1-28 of every 28 day cycle

Also known as: Apalutamide, Enzalutamide

Enzalutamide Exposed - Combination therapy (AR Blockade + Carotuximab); Enzalutamide Naive - Combination therapy (AR Blockade + Carotuximab); Enzalutamide Naive - Monotherapy

Eligibility Criteria

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

You may qualify 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 may not qualify 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.

Sponsors & Collaborators

• Kairos Pharma: collaborator
• Edwin Posadas, MD: lead

Study Sites (3)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

RECRUITING

Huntsman Cancer Institute and Hospital

Salt Lake City, Utah, 84112, United States

RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

apalutamide; enzalutamide; carotuximab

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

• Edwin Posadas, MD FACP

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Trial Recruitment Navigator

CONTACT

310-423-5842; GroupCancerTrialInformation@cshs.org

Edwin Posadas, MD FACP

CONTACT

edwin.posadas@csmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Co-Director, Experimental Therapeutics Program

Study Record Dates

• First Submitted: September 6, 2022
• First Posted: September 9, 2022
• Study Start: December 27, 2023
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 30, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)