A Phase 3 Study to Evaluate the Safety and Efficacy of APL-1202 as a Single-agent Oral Treatment Versus Intravesical Instillation of Epirubicin Hydrochloride in naïve Intermediate-risk NMIBC Patients

Inclusion Criteria: All patients must meet all the following criteria:

• Must be informed of the investigational nature of this study and must provide writteninformed consent
• Age ≥18 years, male or female
• Non-muscle invasive transitional cell carcinoma of the bladder is histologicallyconfirmed by Independent Pathology Review Committee (IPRC). Diagnosis andclassification of intermediate-risk NMIBC is according to 2014 CUA Guideline ofDiagnosis and Treatment of Urological Diseases in China: Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, no CIS. (Note: the above conditions must be met at the same time as a low-risk NMIBC)Intermediate-risk: All tumours not defined in the two adjacent categories (between thecategory of low and high risk) High-risk: Any of the following: ① T1 tumour; ②G3(high-gradeurothelial carcinoma) tumour;③carcinoma in situ (CIS); ④ Multiple, recurrent and large (> 3cm) TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)

• No visible tumor after transurethral resection of bladder tumor (TURBT) on tumor lesion.Some requirements about Re-TURBT are as follows: It is recommended to conduct the secondaryTURBT under following situations: incomplete first TURBT; no muscle tissue found in thefirst TURBT specimen, except Ta G1 (low grade) tumor and CIS only. The secondary TURBT is recommended 2-6 weeks, but better at 4 weeks, after the first TURBT. For subjects undergoing secondary TURBT, they will be enrolled after the second TURBT

• Subjects who never received intravesical instillation (including BCG or intravesicalchemotherapy) prior to enrollment, except single, immediate, post-operativeintravesical chemotherapy.
• Willing to provide pathological tissue specimen for assessment
• ECOG PS ≤ 1
• Patients, who have not received blood transfusion or colony-stimulating factortreatment within 14 days before the examination, must have normal organ and marrowfunction within 42 days of study entry (according to normal range in clinical site). Absolute neutrophil count >1.5×109/L Platelets > 100 ×109/L Hemoglobin > 9.0 g/dL Alkalinephosphatase < 2.5 ULN GFR (Cockcroft-Gault formula calculated) ≥ 50 mL/min Total bilirubin,alanine aminotransferase or aspartate aminotransferase< 1.5 ULN INR <1.5, except forsubjects receiving anticoagulation therapy
• Female should be either surgically sterilized or menopause or agree to use effectivecontraceptive measures during treatment. Women of reproductive age must have anegative result of pregnancy test during the screening period (pregnancy test will benot required if one of the following situations exists: the subject has undergonesterilization such as hysterectomy and/or bilateral oophorectomy, has no menstruationfor 12 months and been diagnosed as menopause based on factors such as age). However,pregnancy tests are required for patients with bilateral fallopian tube ligation.
• Male subjects should be either surgically sterilized or agreed to use effectivecontraceptive measures. From signing the informed consent, subjects must takecontinuous measures until 3 months after the end of the treatment of trial. Thedefinition of effective contraceptive measures will be based on the principalinvestigator(PI) or appointed delegate.
• Expected life expectancy is more than 48 months

Exclusion Criteria: The presence of any of the following will exclude a patient from study enrollment:

• Low-risk: Primary, solitary, TaGl (PUNLMP, low-grade urothelial carcinoma), <3cm, noCIS. (PS: the above conditions must be met at the same time as a low-risk NMIBC)
• High-risk: Any of the following: ① T1 tumour; ②G3(high-grade urothelial carcinoma)tumour;③carcinoma in situ (CIS); ④ Multiple, recurrent and large (> 3 cm)TaG1G2(low-grade urothelial carcinoma) tumours (all features must be present)
• Tumors of T2 stage or more serious
• The histological types are mainly non-urothelial carcinomas such as squamous cellcarcinoma and adenocarcinoma
• Urothelial carcinoma outside the bladder (renal pelvis, ureter or urethra)
• Received intravesical therapy in last TURBT/cystoscopy prior to treatment period, butnot including immediate intravesical therapy once (the subjects who received theimmediate intravesical therapy need to be recorded in e-CRF)
• Received surgery (not includes TURBT/cystoscopy), radiation therapy, or systemictherapy within 6 weeks before enrollment
• Malignancies within 2 years with exception of currently treated basal cell, squamouscell carcinoma of the skin, or carcinoma "in-situ' of the cervix
• Grade 3 (according to the NCI CTCAE 5.0) hemorrhage in any part of body within 6 weeksbefore starting the treatment of trial
• Any of the following within 6 months prior to study drug administration: myocardialinfarction, severe/unstable angina, coronary/peripheral artery bypass graft,symptomatic congestive heart failure, cerebrovascular accident or transient ischemicattack, or pulmonary embolism
• Hypertension that cannot be controlled by medications (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg)
• Uncontrolled active infections before starting the treatment of trial, such as acutepneumonia, active hepatitis B, etc.
• Dysphagia or known drug absorption disorders
• Anuria
• One week prior to enrollment, having gross hematuria
• Active duodenal ulcers, ulcerative colitis and other gastrointestinal diseases orother conditions that the investigator may determine to cause gastrointestinalbleeding or perforation
• The risk of participation or administration may increase, judged by investigator, orother severe acute or chronic medical conditions may interfere with the interpretationand judgment of results
• or optic nerve disorders
• Subjects have optic nerve disorders and cataracts, or other related medical history
• Pregnancy or breastfeeding. Female patients with reproductive potential have apositive pregnancy test prior to enrollment
• Psychological or mental abnormality, subjects are estimated to have insufficientadherence to this clinical study
• Four weeks prior to enrollment, participate in other clinical trials
• Patients who had previously received anthracycline for systemic chemotherapy