Patient enrollment has been completed for the global phase 3 TAVT45CO2 trial, which is 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 TAVT45CO2 study is comparing the pharmacodynamic effect and safety profile of TAVT-45 versus the standard abiraterone formulation. Tavanta Therapeutics, the developer of TAVT-45, expects to have topline results from the study by the end of this year.
"The current standard of care treatment for metastatic prostate cancer 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," Kenneth M. Kernen, MD, study investigator and partner in the Michigan Institute of Urology, stated in a press release. "
Dysphagia is an issue for many – and it occurs more frequently in elderly patients. If TAVT-45 proves successful in this trial, clinicians may soon have access to an alternative, easy-to-drink formulation of abiraterone acetate with improved bioavailability and reduced systemic variability, which may ultimately help patients achieve better clinical outcomes," added Kernen.
The open-label phase 3 TAVT45CO2 study (NCT04887506) has a target enrollment of 107 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 are being 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 standard formulation of abiraterone currently has FDA-approved indications for both metastatic CSPC and metastatic CRPC.
“On behalf of Tavanta, we would like to thank the clinical study site investigators and the patients who are participating in and supporting this pivotal trial, especially in light of the ongoing challenges of the COVID-19 pandemic. We look forward to completing the dosing and follow-up phases of the study," Lynne Powell, chief executive officer of Tavanta, stated in the press release. "As we work to complete this registrational trial for TAVT-45, we will begin preparing for the submission of our New Drug Application to the US Food and Drug Administration in the third quarter of 2023, while also evaluating strategic options for commercialization of TAVT-45."
1. Tavanta Therapeutics Announces Completion of Enrollment in Pivotal Phase 3 Trial of TAVT-45 for the Treatment of Metastatic Prostate Cancer. Published online August 1, 2022. Accessed August 1, 2022. https://yhoo.it/3PTK8wS
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