Efficacy and Safety of LY01005 in Patients With Prostate Cancer Compared to ZOLADEX®

A Multicenter, Randomized, Open-Label Phase Ⅲ Trial to Compare Efficacy and Safety of Goserelin Acetate Sustained-Release Microspheres for Injection (LY01005) and ZOLADEX® in Patients With Prostate Cancer

This is a multicenter, randomized, open-label, active comparator-controlled phase Ⅲ trial to compare efficacy and safety of Goserelin Acetate Sustained-Release Microspheres for Injection (LY01005) and ZOLADEX® in patients with prostate cancer.

This is a multicenter, randomized, open-label, active comparator-controlled phase Ⅲ trial using non-inferior design. A total of 290 patients with prostate cancer who were suitable for endocrine therapy were enrolled into the screening period from D-21 to D-10 before administration. Eligible subjects were treated with bicalutamide tablets (Casodex®, 50 mg/day) from D-10 (± 3d) before administration and randomized in a 1:1 ratio to receive LY01005 3.6 mg or ZOLADEX® 3.6 mg after completion of pretreatment. All subjects were administered once every 28 days for three doses until intolerable toxicity, disease progression requiring other anti-tumor treatments, withdrawal of consent, loss to follow-up, death or the end of the whole study. Blood samples were collected at the specified time points of the screening period, before/behind each dose to detect serum testosterone, LH, FSH and PSA. Safety evaluation (including vital signs, physical examination, laboratory tests, 12 ECG, adverse events, etc.) was conducted as required in the protocol.

Inclusion Criteria:

1. 50 years or older.
2. Patients with pathological confirmed prostate cancer suitable for endocrine therapy (except for neoadjuvant endocrine therapy), including those who are suitable for endocrine therapy (such as patients with biochemical recurrence after adjuvant endocrine therapy and radical therapy) following radical therapy.
3. Serum testosterone level ≥ 1.50 ng/mL (5.21 nmol/L) at the screening visit (based on the test results of research centers).
4. Life expectancy of at least 9 months.
5. ECOG score of ≤ 2.
6. Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L, platelet count ≥ 100 x 10^9/L, white blood cell count ≥ 3 x 10^9/L, and hemoglobin ≥ 90 g/L at the screening visit.
7. Total bilirubin (TBIL) ≤ 1.5×ULN, both ALT and AST ≤ 2.5×ULN (or ≤ 5.0×ULN for patients with liver metastases) at the screening visit.
8. Calculated creatinine clearance (Cockcroft-Gault formula) of ≥ 30 mL/min at the screening visit.
9. Patients who voluntarily sign an IRB-approved informed consent form before the screening visit, are willing to abide by the restrictions of the study, and complete the prescribed examinations.

Exclusion Criteria:

1. Patients with prostate cancer who receive previous or ongoing endocrine therapy (surgical castration or other endocrine therapy including GnRH receptor agonists, GnRH receptor antagonists, anti-androgens, estrogens, megestrol acetate, etc.), except for patients with prostate cancer undergoing prostatectomy, radiotherapy or cryotherapy who have received neoadjuvant/adjuvant endocrine therapy for no more than 6 months and discontinued the above therapy more than 6 months before screening.
2. Has received prostatic surgery within 4 weeks prior to the Screening Visit, or plan to receive surgical treatment during the trial.
3. Patients with confirmed or suspected hormone-resistant prostate cancer.
4. Has previously received hypophysectomy or adrenalectomy, or who have pituitary lesions.
5. Has received 5-α reductase inhibitors (finasteride, dutasteride, eridasteride, etc.) within 1 month before the first dose.
6. Has previously received goserelin.
7. Has received an investigational drug, an investigational biological product or an investigational medical device, and discontinued within 1 month or 5 half-lives of the corresponding drug before the screening visit, whichever is longer.
8. History of severe asthma, anaphylaxis, or severe urticaria and/or angioedema.
9. History or presence of another malignancy, other than surgically removed squamous/basal cell carcinoma of the skin, within the last 5 years.
10. History of the following medical histories within 6 months: myocardial infarction, unstable angina, coronary revascularization, New York Heart Association (NYHA) class ≥ II cardiac insufficiency, severe unstable arrhythmia; Or the presence of arrhythmia requiring treatment at the screening period.
11. Hypertensive patients with poor blood pressure control after medication (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg at the screening visit).
12. Has received coumarin anticoagulants.
13. Patients with type 1 diabetes or type 2 diabetes with poor glycemic control (glycosylated hemoglobin > 8% at the screening visit).
14. Has congenital long QT syndrome or QT/QTc interval prolongation (QTc ≥ 450 ms) at the screening visit; Or has received drugs that may prolong QT/QTc interval at the screening visit.
15. Alcoholics, drug addicts or drug abusers.
16. Patients of childbearing potential who refuse using effective contraception during the entire trial.
17. Patients with viral hepatitis B who are taking anti-hepatitis B virus (HBV) drugs or need drug treatment (those who need drug treatment must meet the following 2 conditions at the same time: 1. HBV DNA level: HBeAg-positive patients, HBV DNA ≥ 20,000 IU/ml [equivalent to 10^5 copies/mL]; HBeAg-negative patients, HBV DNA ≥ 2,000 IU/ml [equivalent to 10^4 copies/mL]; 2. ALT ≥ 2 x ULN).
18. Patients who are seropositive for hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV) antibody.
19. Known to be allergic to the active ingredients or any excipients of the investigational drug, or other GnRH analogues.
20. Other conditions considered unsuitable for enrollment by the investigator (such as spinal cord compression due to prostate cancer metastatic lesions of pyramid, pulmonary interstitial disease or other serious diseases).