This is an open-label, multi-site study of apalutamide 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 apalutamide and apalutamide + 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 apalutamide 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 (prostate-specific antigen) on a contemporary ARSI (Androgen receptor (AR) signaling inhibitor: abiraterone, enzalutamide, darolutamide). Bicalutamide, nilutamide, and flutamide will not be considered as contemporary ARSIs
Patient must have had 1 and can have up to 2 prior AR targeted therapy with the exception of apalutamide.
Patients must decline or be ineligible for taxane therapy in the opinion of the treating physician.
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 and/or carotuximab)
Non-PSA producing prostate cancers such as small cell prostate cancers or those prostate cancers which exhibit radiographic progression without PSA rise
Prior use of apalutamide
Other prior malignancy requiring active anticancer therapy
Prior exposure to carotuximab or any CD105 targeted antibody
Parallel
Apalutamide
DrugStandard of care Apalutamide 240 mg 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 apalutamide and apalutamide + 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 apalutamide
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 apalutamide + carotuximab
Participants of the combination of apalutamide + 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 apalutamide 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
Enviro Therapeutics, Inc.
Collaborator
