A Trial of Durvalumab (MEDI4736) Plus Monalizumab in Non-Muscle-Invasive Bladder Cancer

NCT06503614 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN GU21-551
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

This is a phase 2 open-label two cohort study of durvalumab plus monalizumab in patients with BCG-unresponsive or BCG-exposed CIS NMIBC. Arm A will enroll 43 participants who have cancer in situ (CIS) with or without high grade papillary urothelial cancer. Arm B will enroll 17 participants who do not have cancer in situ (CIS) but do have high grade papillary urothelial cancer. Eligible patients will be enrolled to receive up to 13 cycles of monthly combination of monalizumab and durvalumab. Both monalizumab and durvalumab will be administered intravenously (IV) every 28 days.

Conditions

Non-muscle Invasive Bladder Cancer; Non-Muscle Invasive Bladder Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Complete Response

  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 Outcomes (7)

• Incidence of treatment related Adverse Events

  12 months

• Progression-free Survival (PFS)

  36 months

• Overall Survival (OS)

  36 months

• Event Free Survival

  36 months

• Cyctectomy Free Survival

  36 months

Study Arms (2)

Cohort A: Durvalumab and Monalizumab for CIS +/- high grade papillary urothelial cancer

EXPERIMENTAL

Durvalumab 1500mg IV and monalizumab 1500mg IV will be administered to all patients once every 4 weeks. A cycle is equal to 4 weeks. This will continue until disease progression, unacceptable toxicity, or for a maximum of 1 year.

Drug: Durvalumab; Drug: Monalizumab

Cohort B: Durvalumab and Monalizumab for high grade papillary urothelial cancer without CIS

EXPERIMENTAL

Durvalumab 1500mg IV and monalizumab 1500mg IV will be administered to all patients once every 4 weeks. A cycle is equal to 4 weeks. This will continue until disease progression, unacceptable toxicity, or for a maximum of 1 year.

Drug: Durvalumab; Drug: Monalizumab

Interventions

Monalizumab DRUG

Monalizumab 1500mg IV

Cohort A: Durvalumab and Monalizumab for CIS +/- high grade papillary urothelial cancer; Cohort B: Durvalumab and Monalizumab for high grade papillary urothelial cancer without CIS

Durvalumab DRUG

Durvalumab 1500mg IV

Also known as: MEDI 4736

Cohort A: Durvalumab and Monalizumab for CIS +/- high grade papillary urothelial cancer; Cohort B: Durvalumab and Monalizumab for high grade papillary urothelial cancer without CIS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years at the time of consent.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. Able and willing to provide written informed consent.
• Eastern Cooperative Oncology Group scores ≤ 1 within 28 days prior to registration.
• Non-muscle-invasive bladder cancer
• Cohort A: CIS +/- high grade papillary urothelial cancer (Ta or T1) after 3-mo evaluation after induction BCG.
• Cohort B: High grade papillary urothelial cancer (Ta or T1) after 3-mo evaluation after induction BCG.
• Mixed variant histology (adenocarcinoma, squamous cell carcinoma) is eligible, but pure variant histology is ineligible. NOTE: Pathology report required for documentation purposes.
• Patients can have BCG-unresponsive or BCG-exposed NMIBC11. Adequate BCG therapy is defined as completing at least induction BCG (≥ 5 doses) and the first round of maintenance or second induction course BCG (≥ 2 doses). The subsequent round of BCG, either maintenance or repeat induction, must be given within 6 months of initial induction BCG.
• BCG-unresponsive is defined as high grade persistent or recurrent NMIBC that has not achieved a disease-free status after an adequate course of BCG therapy. This includes patients with:
• Persistent or recurrent high-grade tumors (Ta/T1) or carcinoma in situ (CIS) within 6 to 12 months of completing adequate BCG therapy.
• Recurrent high-grade papillary disease within 6 months of BCG therapy.
• High-grade T1 disease found at the first evaluation after BCG induction therapy alone.
• BCG-exposed is defined as high grade NMIBC that has recurred after an initial response or is still present after initial treatment, but recurrence is never too late to be considered "BCG-unresponsive". This includes patients with:
• High-grade recurrence between 12 and 24 months after adequate BCG therapy.
• Recurrence within 24 months of inadequate BCG therapy.

You may not qualify if:

• Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137).
• Prior CIS of the ureters or prostatic urethra within 24 months prior to registration.
• Evidence of metastatic disease on imaging (CT or MRI) of the abdomen and pelvis within 90 days of registration.
• Body weight ≤ 30 kg.
• History of allogeneic organ transplantation.
• History of another primary malignancy other than muscle-invasive bladder cancer less than 5 years prior to Day 1 of this trial, with the exception of a malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of study drug and of low potential risk for recurrence. Other exceptions include those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer (non-melanoma skin cancer) or lentigo maligna without evidence of disease, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ without evidence of disease treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate specific antigen \[PSA\] ≤ 10 mg/mL, etc.)
• Currently participating in or has participated in a trial of an investigational agent within 4 weeks prior to the first dose of study treatment or 5 half-lives, whichever is longer without recovery of clinically significant toxicities from that therapy.
• Active or prior autoimmune or inflammatory disorders requiring systemic treatment within 24 months prior to registration. Autoimmune or inflammatory disorders include, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease(colitis or Crohn's disease), diverticulitis (with the exception of diverticulosis),antiphospholipid syndrome, Sarcoidosis syndrome, or Wegener's syndrome (granulomatosis with polyangiitis, Graves' disease, hypophysitis, uveitis, etc), Sjogren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. NOTE: The following are exceptions to this criterion: Patients with vitiligo or alopecia, hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement. Any chronic skin condition that does not require systemic therapy. Patients without active disease in the last 5 years may be included but only after consultation with the study physician. Patients with celiac disease controlled by diet alone.
• A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration. NOTE: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• Known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Active known tuberculosis.
• Symptomatic herpes zoster within the past 30 days.
• Active infection requiring systemic therapy. NOTE: Prophylactic antibiotics are permitted. Treatment for a UTI is allowed but must be deemed adequately treated by the treating physician prior the start of C1D1.
• History of idiopathic pulmonary fibrosis or organizing pneumonia.
• History of (non-infectious) pneumonitis that required steroids or have current pneumonitis.

Sponsors & Collaborators

• John Sfakianos: lead
• AstraZeneca: collaborator
• Icahn School of Medicine at Mount Sinai: collaborator
• Bladder Cancer Advocacy Network: collaborator

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms

Interventions

durvalumab; monalizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• John Sfakianos, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

John Sfakianos, MD

CONTACT

212-659-9375; john.sfakianos@mountsinai.org

Ahran Lee

CONTACT

317-634-5842; alee@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: July 10, 2024
• First Posted: July 16, 2024
• Study Start: February 24, 2025
• Primary Completion (Estimated): December 22, 2027
• Study Completion (Estimated): December 22, 2032
• Last Updated: April 8, 2026

Record last verified: 2026-04

Locations

US (4)