A Trial of Durvalumab (MEDI4736) Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer
NCT Number: NCT06503614
Acronym: ENHANCE
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Non-muscle Invasive Bladder Cancer|Non-Muscle Invasive Bladder Urothelial Carcinoma
Interventions: DRUG: Durvalumab|DRUG: Monalizumab
Sponsor: John Sfakianos
Collaborators: AstraZeneca|Icahn School of Medicine at Mount Sinai
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-12
Completion Date: 2026-12

Summary:
This is a phase 2 open-label two cohort study of durvalumab plus monalizumab in patients with BCG-unresponsive or BCG-exposed CIS non-muscle invasive bladder cancer (NMIBC). BCG-exposed NMIBC encompasses BCG resistance (presence of high-grade Ta, TI or carcinoma in situ \[CIS\] at 3-mo evaluation after induction BCG). Arm A will enroll participants who have cancer in situ (CIS) with or without high grade papillary urothelial cancer. Arm B will enroll participants who do not have cancer in situ (CIS) but do have high grade papillary urothelial cancer.

Primary Outcome Measures: Complete Response Rate, Complete response rate (CRR) is defined as the proportion of patients who achieve CR. Complete response will be determined by bladder biopsy and urinary cytology for malignancy for subjects with a CIS component at 6 months CT/MRI urography will be used to rule out extravesical disease. (Cohort A), 6 months
Secondary Outcome Measures: Incidence of treatment related Adverse Events, Safety will be determined by summarizing all treatment related adverse events according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5. (Cohort A and B), 12 months|Progression-free Survival (PFS), Progression-free survival (PFS) will be measured from the date of study registration to the date of progression or death due to any cause, whichever occurs first. Surviving patients without any documented progression will be censored at the date of last known contact. Progression will be defined as the development of muscle invasive bladder cancer or metastatic urothelial cancer (nodal and/or distant). (Cohort A), 36 months|Overall Survival (OS), Overall survival (OS) will be measured from the date of study registration to date of death due to any cause. Surviving patients will be censored at the date of last known contact. (Cohort A), 36 months|Event Free Survival, Event-free survival will be measured from the date of study registration to the first documentation of an event. Patients without documented events and who are still alive, will be censored at last disease assessment. Patients who start any subsequent anti- cancer therapy without any reported events will be censored at their last disease assessment. (Cohort A), 36 months|Cyctectomy Free Survival, Cystectomy-free survival will be measured from the date of study registration to the date of cystectomy for all patients. (Cohort A), 36 months|Duration of Response (DOR), Duration of response (DOR) will be measured from the time a patient had a documented response (the time would start at the time a response was first noted) until disease-progression. This analysis will only include those patients in the CIS population who achieve a response. Patients who are alive and without a documented progression at the time of analysis will be censored at the time of the last disease status evaluation. (Cohort A), 36 months|Recurrence-free Survival, Recurrence-free survival will be measured from the date of study registration to the date of recurrence. Recurrence will be defined as the development of high-grade bladder cancer for patients without a CIS component at baseline. (Cohort B), 12 months