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.
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.
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
Parallel
AR Blockade
DrugStandard of care Apalutamide 240 mg / Enzalutamide 160mg administered orally and daily on Days 1-28 of every 28 day cycle
Carotuximab
DrugCarotuximab 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.
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.
Incidence of Adverse events (grade 3 or higher) related to carotuximab and AR blockade
Grade 3 or above treatment related adverse events as assessed per NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Overall radiographic response rate (ORR) of the combination of AR blockade + carotuximab
Participants of the combination of AR blockade + carotuximab, with confirmed complete response (CR) or partial response (PR) per RECIST v.1.1 and Prostate Cancer Working Group 3
Proportion of patients resistant to AR blockade benefit from the addition of carotuximab
Participants of the monotherapy group that crossover to combination therapy at progression, with confirmed complete response (CR) or partial response (PR) per RECIST v.1.1 and Prostate Cancer Working Group 3
Overall radiographic response rate (ORR) in the overall population
Determined by confirmed complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) and Prostate Cancer Working Group 3
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Edwin Posadas, MD
Lead sponsor
Cedars-Sinai Medical Center
Sponsor institution
Kairos Pharma
Collaborator
