A Study of Nivolumab Plus Bempegaldesleukin (Bempeg/NKTR-214) vs Nivolumab Alone vs Standard of Care in Participants With Bladder Cancer That May Have Invaded The Muscle Wall of the Bladder and Who Cannot Get Cisplatin, A Type of Medicine Given To Treat Bladder Cancer

Bristol-Myers Squibb (BMS)

Status and phase: Completed; Phase 3

Conditions: Bladder Tumor; Bladder Cancer; Muscle-Invasive Bladder Cancer

Treatments: Biological: Nivolumab; Procedure: Radical cystectomy (RC); Biological: Bempegaldesleukin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04209114

18-214-13 (Other Identifier)

2018-002676-40 (EudraCT Number)

CA045-009

Details and patient eligibility

About

The purpose of the study is to see if treatment with nivolumab plus bempegaldesleukin or nivolumab alone, before and after surgery to remove the bladder, is more effective than surgery alone in participants with high-risk urothelial cancer, including muscle-invasive bladder cancer who are not able to receive cisplatin chemotherapy.

Enrollment: 114 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Urothelial carcinoma (UC) of the bladder, clinical stage T2-T4aN0, M0 or T1-T4aN1, M0, diagnosed at transurethral resection of bladder tumor (TURBT)

• Must be deemed eligible for Radical Cystectomy (RC) by urologist, and must agree to undergo RC. For arms A and B, participants must agree to undergo RC after completion of neoadjuvant therapy.

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Cisplatin-ineligible participants will be defined by any one of the following criteria:

  i) Impaired renal function (glomerular filtration rate [GFR] ≥ 30 but < 60 mL/min) ii) GFR should be assessed by direct measurement (ie, creatinine clearance) or, if not available, by calculation from serum/plasma creatinine (Cockcroft-Gault formula) iii) Common Terminology Criteria for Adverse Events (CTCAE) version 5, ≥ Grade 2 hearing loss (assessed per local SOC).

iv) CTCAE version 5, ≥ Grade 2 peripheral neuropathy.

• Documented Left Ventricular Ejection Fraction (LVEF) more than 45%

Exclusion criteria

• Clinical evidence of ≥ N2 or metastatic bladder cancer
• Prior systemic therapy, radiation therapy, or surgery for bladder cancer other than TURBT or biopsies is not permitted. Prior Bacillus Calmette-Guerin (BCG) or other intravesicular treatment of non-muscle invasive bladder cancer (NMIBC) is permitted if completed at least 6 weeks prior to initiating study treatment.
• Evidence of urothelial carcinoma (UC) in upper urinary tracts (ureters or renal pelvis) or history of previous MIBC
• History of pulmonary embolism (PE), deep vein thrombosis (DVT), or prior clinically significant venous or non-CVA(cerebrovascular accident)/TIA (Transient ischemic attack) arterial thromboembolic event
• Known cardiovascular history, including unstable or deteriorating cardiac disease within the previous 12 months (including unstable angina or myocardial infarction, congestive heart failure or uncontrolled clinically significant arrhythmias)

Other protocol-defined inclusion/exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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114 participants in 3 patient groups

Arm A: Combination Therapy

Experimental group

Description:

Neoadjuvant (pre-surgical treatment) nivolumab + bempeg, followed by radical cystectomy (RC), followed by adjuvant (post-surgical treatment) nivolumab + bempeg

Treatment:

Biological: Bempegaldesleukin

Procedure: Radical cystectomy (RC)

Biological: Nivolumab

Arm B: Monotherapy

Experimental group

Description:

Neoadjuvant nivolumab, followed by RC, followed by adjuvant nivolumab

Treatment:

Procedure: Radical cystectomy (RC)

Biological: Nivolumab

Arm C: Standard-of-care

Other group

Description:

RC alone, without neoadjuvant or adjuvant therapy

Treatment:

Procedure: Radical cystectomy (RC)