TAVT-45 (Abiraterone Acetate) Granules in Patients With Prostate Cancer

Phase 3 Study Investigating the Efficacy and Safety of TAVT-45 (Abiraterone Acetate) Granules for Oral Suspension (Novel Abiraterone Acetate Formulation) Relative to a Reference Abiraterone Acetate Formulation in Patients With mCSPC & mCRPC

The purpose of this study is to investigate the safety and efficacy of a new formulation of an existing drug product called TAVT-45 in patients with metastatic prostate cancer.

This is a Phase 3 randomized, open-label study to evaluate the pharmacodynamic effect and safety profile of TAVT-45 compared to Zytiga (reference abiraterone acetate formulation, hereafter referred to as R-AA) in patients with high-risk metastatic castrate sensitive prostate cancer (mCSPC) and metastatic castrate resistant prostate cancer (mCRPC). Randomization was stratified by prostate cancer population (CSPC vs CRPC) and baseline testosterone (<10 vs ≥ 10 ng/dL). Patients were treated for 84 days and randomized into one of two groups in a 1:1 ratio:

• TAVT-45: Administered twice daily as 1 x sachet containing TAVT-45 (250 mg abiraterone acetate), reconstituted in water or specified fruit juice (orange juice), + Prednisone (5 mg once or twice daily, depending on prostate cancer population)
• R-AA: Administered once daily as (2 x 500 mg Zytiga tablets) + Prednisone (5 mg once or twice daily, depending on prostate cancer population)

Inclusion Criteria:

1. Written informed consent obtained prior to any study-related procedure being performed

2. Male patients at least 18 years of age or older at time of consent

3. Pathologically confirmed adenocarcinoma of the prostate

4. Ongoing therapy with a gonadotropin releasing hormone (GnRH) agonist or antagonist (unless patient has already had a bilateral orchiectomy) AND serum testosterone level <50 ng/dL at screening

5. Have either metastatic CSPC or metastatic CRPC (per protocol definitions).

6. The following prior treatments and/or surgery for prostate cancer are allowed:

   1. CSPC:

      • Up to 90 days of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists/antagonists or orchiectomy with or without concurrent anti-androgens prior to patients' randomization is permitted
      • Patients may have one course of palliative radiation or surgical therapy to treat symptoms resulting from metastatic disease (e.g., impending cord compression or obstructive symptoms) if administered prior to randomization
      • Radiation or surgical therapy that was not initiated 4 weeks after the start of ADT or orchiectomy

   2. CRPC:

      • Previous chemotherapy with docetaxel for metastatic disease with treatment completed at least 1 year prior to screening

7. Discontinuation of flutamide or nilutamide, and other anti-androgens prior to the start of study medication; discontinuation of bicalutamide prior to start of study medication

8. Discontinuation of strong cytochrome P450 3A4 (CYP3A4) inducers at least 4 weeks prior to start of study medication

9. Discontinuation of radiotherapy prior to start of study medication

10. Discontinuation of herbal supplements at least 4 weeks prior to the first dose of study medication and for the duration of the trial.

11. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at screening

12. Normal organ function with acceptable initial laboratory values within the screening period:

    • Absolute neutrophil count (ANC): ≥ 1,500/μl
    • Albumin: ≥ 3.0g/dL
    • Hemoglobin: ≥ 9g/dL
    • Platelet count: ≥ 100,000/μl
    • Serum Creatinine: ≤ 3.0 x the institutional upper limit of normal (ULN)
    • Potassium: ≥ 3.5 mmol/L (within institutional normal range)
    • Bilirubin: ≤ 1.5 ULN (unless documented Gilbert's disease)
    • Aspartate aminotransferase (AST): ≤ 2.5 x ULN
    • Alanine aminotransferase (ALT): ≤ 2.5 x ULN

13. Life expectancy of at least 6 months at screening

14. Patients engaged in sex with women of child-bearing potential agree to use a condom plus another effective contraception method. Patients agree to use a condom when engaged in any sexual activity, including sex with a pregnant woman. These restrictions will apply from the time informed consent is provided until 3 weeks after the last dose of study medication is taken.

15. Patient is willing and able to comply with all protocol requirements

Exclusion Criteria:

1. For mCSPC patients: any prior pharmacotherapy, radiation therapy, or surgery for metastatic prostate cancer not specified as allowable treatment in Inclusion Criterion 6. For example, prior therapy with apalutamide or enzalutamide is prohibited as well as therapy with an investigational agent as described in Exclusion Criterion 16.

2. For mCRPC patients:

   • Prior treatment with abiraterone or enzalutamide is prohibited
   • Previous chemotherapy is prohibited with exception of docetaxel treatment as specified in the inclusion criteria 6.

3. Initiation of bisphosphonate or denosumab therapy within 4 weeks prior to the start of study drug/reference product. Patients who are on a stable dose of these medications for at least 4 weeks at the time of starting study drug/reference product will be eligible.

4. Therapy with estrogen within 4 weeks prior to the start of study drug

5. Use of systemic glucocorticoids equivalent to >10 mg prednisone daily. Patients who have discontinued or reduced dosing to the equivalent of ≤ 10 mg prednisone daily within 14 days prior to the start of study drug are eligible

6. Known, symptomatic metastases to the brain or central nervous system involvement (patients with asymptomatic and neurologically stable disease for the past 4 weeks will be permitted)

7. History of adrenal gland dysfunction defined as requiring treatment for adrenal insufficiency

8. History of other malignancy within the previous 2 years (no longer being actively treated), with the exceptions of basal cell carcinoma, nonmuscle invasive bladder cancer that has been treated and is under surveillance, or other in-situ cancers with a low likelihood of recurrence

9. Major surgery within 4 weeks prior to the start of study drug

10. Known gastrointestinal disease or condition that could impair absorption inclusive of gastrocolic fistula, gastroenterostomy, biliary obstruction, cirrhosis, chronic pancreatitis or pancreatic cancer, cystic fibrosis, lactate deficiency, amyloidosis, celiac disease, Crohn's disease, radiation enteritis, intestinal resection, and history of bariatric surgery

11. Known history of human immunodeficiency virus or seropositive test for hepatitis C virus (HCV) or hepatitis B surface antigen (HBsAg) (note: HCV patients with undetectable viral load will be eligible)

12. Poorly controlled diabetes, defined as hemoglobin A1c (HbA1c) > 8% within the past 12 months

13. Uncontrolled hypertension at screening

14. History of New York Heart Association class III or IV heart failure

15. Serious concurrent illness, including psychiatric illness, that could interfere with study participation

16. Receipt of another investigational agent within 4 weeks or 5 x the treatment half-life, whichever is longer, of treatment start.

17. Known hypersensitivity or allergy to abiraterone acetate, prednisone or any excipients in the study drugs

18. In the opinion of the investigator, participation in the trial would prevent the patient from receiving local standard-of-care treatment for metastatic prostate cancer, if clinically indicated, after completion of the trial

19. Other condition which, in the opinion of the Investigator, would preclude participation in this trial.