The first patient has been dosed in a Phase 1/2a clinical trial that will assess TRACON Pharmaceuticals’ TRC253 for treating metastatic castration-resistant prostate cancer (mCRPC), a form that has developed resistance against other therapies.
TRACON was able to file an Investigational New Drug application with U.S. regulators quickly, “open multiple sites, and dose TRC253 in a Phase 1/2 trial following the establishment of our strategic licensing collaboration with Janssen,” Dr. Charles Theuer, president and CEO of TRACON, said in a press release. “We think TRC253 has the potential to be a best-in-class androgen receptor antagonist, and address an unmet medical need in the treatment of men with metastatic castration-resistant prostate cancer who develop resistance to androgen receptor inhibitors.”
The Phase 1/2a trial (NCT02987829) will be a multi-center, first-in-human, open-label, dose-escalation study. It will evaluate TRC253’s effectiveness, safety, pharmacodynamics and pharmacokinetics in up to 80 men with mCRPC. Pharmacodynamics refers to how a drug affects the body, while pharmacokinetics refers to how the body impacts a drug.
In Phase 1 of the study, patients will receive escalating doses of TRC253 to determine a recommended Phase 2 dose. Phase 1 will also look at how TRC253 affects patients’ PSA levels. Levels of PSA, or prostate-specific antigens, are a key biomarker of prostate cancer.
Phase 2, the trial’s dose expansion phase, will include two groups of 30 patients each. Cohort 1 will consist of patients with the androgen receptor mutation AR F876L, and Cohort 2 will be patients without the mutation. TRC253 is an androgen receptor antagonist, which means it suppresses androgen receptors.
Those taking part in the trial must have received previous treatment with Xtandi (enzalutamide) or apalutamide. In addition, their PSA levels must show that their cancer resisted these therapies.
Depriving the prostate of androgen is the mainstay therapy for advanced prostate cancer. It leads to lower PSA readings and cancer improvement in more than 90 percent of patients.
The treatment does not cure the disease, however. And most patients eventually become resistant to such hormone therapies.
TRACON developed TRC253 to bind to both normal androgen receptors and mutant forms of the receptor, including AR F876L. Binding to a mutant receptor prevents the activation of several genes that are involved in prostate cancer cell proliferation.