Actively Recruiting
ENHANCE: A Phase 2 Trial of Durvalumab Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer
Led by John Sfakianos · Updated on 2026-04-08
60
Participants Needed
4
Research Sites
261 weeks
Total Duration
On this page
Sponsors
J
John Sfakianos
Lead Sponsor
A
AstraZeneca
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the combination of durvalumab and monalizumab in patients with non-muscle-invasive bladder cancer (NMIBC) who have either carcinoma in situ (CIS) or high-grade papillary urothelial cancer that is unresponsive or exposed to BCG treatment. This phase 2 open-label study aims to assess how these treatments work together in two patient groups based on their cancer type, with a focus on cases that have not responded well to prior BCG therapy. Participants will receive both durvalumab and monalizumab intravenously every 28 days, with each treatment cycle lasting four weeks. Treatment will continue monthly for up to one year or until the cancer progresses or unacceptable side effects occur. There are two cohorts: Cohort A includes patients with CIS with or without high-grade papillary urothelial cancer, and Cohort B includes patients with high-grade papillary urothelial cancer without CIS. During the study, participants will undergo regular assessments including cystoscopy, urine cytology, tumor tissue collection, and evaluations of their overall health and organ function. Researchers will measure outcomes such as complete response at six months, progression-free survival, overall survival, and treatment-related side effects. Monitoring will continue up to 36 months for long-term outcomes, with safety and response evaluated throughout the treatment and follow-up periods.
CONDITIONS
Brief Title
A Trial of Durvalumab (MEDI4736) Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Age 18 years or older at the time of consent
- Willing and able to follow study protocol, including treatments and appointments, and provide informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 days before registration
- Diagnosed with non-muscle-invasive bladder cancer
- Cohort A: Carcinoma in situ (CIS) with or without high-grade papillary urothelial cancer after BCG induction evaluation
- Cohort B: High-grade papillary urothelial cancer without CIS after BCG induction evaluation
- Mixed variant histology allowed; pure variant histology excluded
- BCG-unresponsive or BCG-exposed non-muscle-invasive bladder cancer with adequate prior BCG therapy
- Up to 2 prior therapy lines for NMIBC allowed; prior PD-1/PD-L1 inhibitors excluded
- Unfit for or refusing radical cystectomy
- Complete tumor resection within 60 days before registration; cystoscopy or TURBT without papillary tumor and urine cytology negative except for CIS
- Restaging TURBT with uninvolved muscularis propria for T1 tumors within 60 days prior to registration
- Baseline tumor tissue available for study
- Adequate organ function based on blood counts and liver, kidney tests within 28 days before registration
- Negative pregnancy test for females of childbearing potential and agreement to use contraception
- Men agree to use contraception
- Life expectancy of at least 12 weeks
You will not qualify if you...
- Prior treatment with PD-1, PD-L1, PD-L2, or other T-cell receptor agents
- CIS of ureters or prostatic urethra within 24 months before registration
- Evidence of metastatic disease on recent imaging
- Body weight 30 kg or less
- History of allogeneic organ transplantation
- Other primary cancers within 5 years except certain low-risk or treated cancers
- Participation in other investigational agent trials recently
- Active or recent autoimmune or inflammatory disorders requiring systemic treatment
- Immunodeficiency or recent immunosuppressive therapy
- Psychiatric or substance abuse disorders affecting study cooperation
- Active tuberculosis or recent herpes zoster infection
- Active infection needing systemic treatment
- History of pulmonary fibrosis, pneumonitis, or current pneumonitis
- HIV positive with exceptions for controlled infection
- Active hepatitis infections
- Known allergy to study drugs or excipients
- Recent live vaccinations
- Major surgery within 28 days before study drug
- Uncontrolled illnesses that increase risk or limit consent ability
- Prolonged QT interval on ECG
- Pregnant or breastfeeding women or those unwilling to use birth control
- Significant unresolved toxicities from prior cancer therapies
- Concurrent chemotherapy or biologic cancer treatments
- History of leptomeningeal carcinomatosis
- Prior participation in durvalumab studies
- Recent use of immunosuppressive medications except certain allowed forms
- Steroid use exceeding specified doses unless exceptions apply
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 1 year
Participants receive Durvalumab 1500mg IV and Monalizumab 1500mg IV once every 4 weeks. Treatment continues until disease progression, unacceptable toxicity, or for a maximum of 1 year.
Monthly visits every 4 weeks during treatment
Trial Site Locations
Total: 4 locations
1
Moffitt Cancer Center
Tampa, Florida, United States, 33612
Actively Recruiting
2
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08903
Actively Recruiting
3
Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Actively Recruiting
4
Weill Cornell Medical Center
New York, New York, United States, 10065
Actively Recruiting
Research Team
J
John Sfakianos, MD
A
Ahran Lee
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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