Assessment of Efficacy and Safety of Durvalumab Plus BCG Compared to the Standard Therapy With BCG in Non-muscle Invasive Bladder Cancer

Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment.

Overall survival at 5 years. Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1). Any patient not known to have died at the time of analysis will be censored based on the last recorded date on which the patient was known to be alive

Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death. Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment

Overall survival at 5 years. Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1).

Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death. Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

Disease-free survival using Investigator disease assessments.Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

Proportion of patients alive and disease free at 24 months using Investigator disease assessments. DFS24 is defined as the proportion of patients alive and disease-free at 24 months after randomization, per Investigator disease assessment.

Overall survival (OS) is defined as the time from the date of randomization until death due to any cause regardless of whether the patient withdraws from randomized therapy or receives another anti-cancer therapy (i.e. date of death or censoring - date of randomization +1). The proportion of patients alive at 5 years (OS5)

Any disease-free survival using Investigator disease assessments. Any disease-free survival (aDFS) is defined similarly as DFS, except that aDFS includes recurrence of low/medium risk NMIBC. This will be based on Investigator disease assessments.

Time to MIBC and/or metastatic disease using Investigator disease assessments. Time to MIBC and/or metastatic disease is defined as the time from the date of randomization until the date of first documented MIBC and/or metastatic disease as assessed by Investigator. Time to MIBC and/or metastatic disease does not include deaths. If patients died without MIBC and/or metastatic disease, they will be censored at the time of death. All other censoring rules per DFS analysis will be applied including censoring patients with an event after 2 missed visits and patients with no evaluable disease assessments or no baseline data.

Time to cystectomy using Investigator disease assessments. Time to cystectomy is defined as the time from the date of randomization until the date of cystectomy as reported by Investigator. Patients who died prior to cystectomy will be censored at the time of death.

Patients who have not had a cystectomy at the time of analysis will be censored at the last recorded date on which the patient was known to be alive. No other censoring rules per the DFS analysis will be applied.

Time to development of upper tract urothelial carcinoma using Investigator disease assessments. Time to development of upper tract urothelial carcinoma (TTUTUC) is defined as the time from the date of randomization until the date of development of upper tract urothelial carcinoma as assessed by Investigator using CT urography or ureteroscopy (less common). TTUTUC does not include deaths. Patients who died without upper tract urothelial carcinoma will be censored at the time of death. Other censoring rules per DFS analysis will be applied, including censoring patients with no baseline data but excluding censoring patients with an event after 2 missed visits as evaluation of the upper urinary tract is not part of regular disease assessment and is performed as clinically indicated.

To assess the efficacy of durvalumab + BCG combination therapy compared to BCG (induction and maintenance) for patients with CIS prior to study entry or at baseline cystoscopy.

To assess disease-related symptoms and HRQoL in patients with NMIBC treated with durvalumab + BCG (induction and maintenance) combination therapy and durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone and compared to each other using the EORTC QLQ-C30 questionnaire and the EORTC QLQ-NMIBC24 questionnaire

To assess patient-reported treatment tolerability directly using specific PRO-CTCAE symptoms

To assess the PK of durvalumab when used in combination with BCG treatment

To investigate the immunogenicity of durvalumab when used in combination with BCG treatment