The first patient has been dosed in a global phase 3 trial comparing TAVT-45 granules, a novel formulation of abiraterone acetate (Zytiga), with standard abiraterone in patients with metastatic castration-sensitive prostate cancer (CSPC) or metastatic castration-resistant prostate cancer (CRPC).1,2
The TAVT-45 formulation of abiraterone consists of granules for oral suspension and was created for patients with dysphagia who would have difficulty swallowing a tablet. The phase 3 study is comparing the pharmacodynamic effect and safety profile of TAVT-45 versus the standard abiraterone formulation.
"We are excited to be the first clinical trial site to dose a patient in this trial," Robert Given, MD, a urological oncologist at Urology of Virginia and a study investigator, stated in a press release. "The current standard of care treatment requires patients to ingest multiple large tablets, and under strict fasting conditions due to the risk of increased and highly variable abiraterone exposures with food. In contrast, TAVT-45 granules has the potential to provide the more than 3.2 million prostate cancer patients in the United States, specifically those with dysphagia, with an alternative option that would reduce pill burden."
The open-label phase 3 study is aiming to enroll 108 patients with pathologically confirmed metastatic CSPC or metastatic CRPC and an ECOG performance status of 0 to 2 at screening. Among patients with CRPC, prior chemotherapy with docetaxel is allowed if the patient finished the treatment ≥1 year before enrollment. No other prior chemotherapy is allowed, and patients are excluded from enrollment if they had prior treatment with abiraterone or enzalutamide (Xtandi).
Patients will be randomized to prednisone plus either standard abiraterone (500 mg oral tablet twice daily) or TAVT-45 (250 mg abiraterone granules for oral suspension in a sachet, administered twice daily).
The primary outcome measures are testosterone level averages on day 9 and day 10. The study protocol defines this metric as, “Blood samples collected to measure serum testosterone in order to demonstrate equivalent pharmacodynamic effect between TAVT-45 and reference abiraterone acetate.”
Secondary outcomes measures from the trial include the percent of patients with a PSA level decrease of ≥50% from baseline, overall PSA levels, and several pharmacokinetic metrics. The estimated primary completion date of the study is April 2022.
The standard formulation of abiraterone currently has FDA-approved indications for both metastatic CSPC and metastatic CRPC.
"As one of the most frequently diagnosed cancers in men in the United States, prostate cancer affects a large population of men with unmet medical needs, like dysphagia, and not all can be met with current treatment options," Lynne Powell, chief executive officer of Tavanta Therapeutics, the developer of TAVT-45, stated in the press release. "Importantly, this novel formulation may support improved bioavailability and reduced systemic variability using a lower dose of drug compared to the standard of care, which may ultimately help patients achieve better clinical outcomes."
1. Tavanta Therapeutics Announces First Patient Dosed in Phase 3 Clinical Trial of TAVT-45 (abiraterone acetate) Granules for Oral Suspension, a Novel Formulation of Abiraterone Acetate, for the Treatment of Metastatic Prostate Cancer. Published online May 25, 2021. Accessed May 25, 2021. https://prn.to/3fNM3SP.
2. NIH US National Library of Medicine ClinicalTrials.gov. TAVT-45 (Abiraterone Acetate) Granules in Patients With Prostate Cancer. Last updated May 14, 2021. https://clinicaltrials.gov/ct2/show/NCT04887506