Study of XNW5004 Tablet in Combination With Enzalutamide in Subjects With Metastatic Castration-Resistant Prostate Cancer

Exclusion Criteria27

• Previous anti-tumor therapy meet the following conditions： Ib and IIb: previously received any next generation androgen receptor antagonists (such as enzalutamide, apalutamide, proxalutamide and rezvilutamide, etc.) ； IIa: previously received with enzalutamide or more than 1 novel hormone therapy;
• Prior chemotherapy for castration resistant disease (including but not limited to ADCs);
• Prior exposure to EZH2 inhibitor(s) (including but not limited to tazemetostat and EZH1/2 inhibitors);
• Subjects who received anti-tumor therapies including chemotherapy, immunotherapy, radical radiotherapy, major surgery, targeting therapy and other anti-tumor therapies within 4 weeks or 5 half-lives of the drug (whichever is shorter) before the first dose; or received palliative radiotherapy within 2 weeks before the first dose;
• Plan to receive any other anti-tumor therapy during this trial;
• Subjects who participated in any other clinical trial of anti-tumor therapy within 28 days before the first dosing, and the last dose of other anti-tumor trial drug is within 28 days prior to the first administration of study drug in this trial;
• Central nervous system metastasis or disease;
• Severe bone injury caused by tumor bone metastasis judged by the investigator, including severe bone pain with poor control, pathological fractures of important sites and spinal cord compression that occurred in the past 6 months or are expected to occur in the near future, etc.;
• Subjects who have a history of other malignancies within 3 years prior to enrollment and do not meet the criteria for clinical cure. This exclusion criterion does not apply to skin basal cell carcinoma or squamous cell carcinoma with local treatment methods available and has been cured, superficial bladder cancer, intraductal breast carcinoma in situ, and papillary thyroid carcinoma;
• Subjects who experienced stroke or other serious cerebrovascular diseases within 12 months prior to enrollment;
• Subjects who have impaired heart functions or clinically serious heart disease；
• Have severe systemic active infection;
• Have a history of tuberculosis within 1 year before enrollment, or had an active TB infection more than 1 year before but not received adequate anti-TB treatment;
• Subjects known to be allergic to the study drug or its active ingredients or excipients;
• Subjects taking known moderate or strong inducers and inhibitors of CYP3A within 14 days before the first administration;
• Active autoimmune and inflammatory diseases, such as: systemic lupus erythematosus, psoriasis requiring systemic therapy, rheumatoid arthritis, inflammatory bowel disease, and Hashimoto's thyroiditis, etc., except type I diabetes, Hypothyroidism that can be controlled by replacement therapy alone, hyperthyroidism that is stable under drug control, skin diseases that do not require systemic therapy (eg, vitiligo, psoriasis);
• Past medical history of interstitial lung disease (ILD), history of drug-induced ILD, history of radiation pneumonitis requiring steroid therapy, or evidence of any clinically active ILD;
• Known impaired gastrointestinal (GI) function or GI diseases that may significantly affect the absorption or metabolism of oral drugs; abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before the first administration;
• Human immunodeficiency virus (HIV) positive, syphilis (Anti-TB) positive;
• Known acute or chronic active hepatitis B (HBsAg positive or HBcAb positive, and HBV DNA ≥ 200 IU/mL or ≥ 103 copies/mL) or acute or chronic active hepatitis C (HCV antibody positive and positive for HCV RNA test);
• Subjects who experienced toxicity events during previous anti-tumor treatment and the toxicity has not resolved (the toxicity events has not been graded as ≤ level 1 according to NCI-CTCAE 5.0). Other toxicities that the investigator does not think it will affect the safety assessment of the subject (such as hair loss, etc.) will be allowed;
• Subjects who have clinically symptomatic and uncontrollable pleural or pericardial effusions after multiple times of treatments;
• Subjects who have an allogeneic tissue/ solid organ transplantation;
• Subjects who underwent major surgery within 4 weeks prior to the start of the study treatment, or who are scheduled to undergo a major surgery during the study period (procedures such as puncture or lymph node biopsy is allowed);
• Subjects who have received live vaccines (including attenuated live vaccines) within 28 days prior to the administration of study drug. Inactivated vaccines are permitted.
• A superscan as seen in the baseline bone scan；
• Subjects who are considered unsuitable for the study judged by the investigator.