A Phase 2, single-arm study of bempegaldesleukin (NKTR-214) in combination with nivolumab in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients
Research type
Research Study
Full title
A Phase 2, single-arm study of bempegaldesleukin (NKTR-214) in combination with nivolumab in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients
IRAS ID
260338
Contact name
Robert Huddart
Contact email
Sponsor organisation
Nektar Therapeutics
Eudract number
2018-003636-79
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 8 months, 2 days
Research summary
Summary of Research
Urothelial bladder cancer (UBC) is the most common cancer of the urinary system. The overall survival of a patient with bladder cancer varies based on stage and grade, but for metastatic UBC, the 5-year overall survival is approximately 5%.\nPreferred initial treatment for metastatic UBC is a chemotherapy-based combination therapy regimen using cisplatin. However, approximately 50% of patients are ineligible for cisplatin therapy.\nThe study drugs in this trial are bempegaldesleukin (NKTR-214) and nivolumab given in combination. NKTR-214 has not been approved by any regulatory authority. Nivolumab is approved for second-line treatment of metastatic urothelial cancer in the US, UK, and some other European countries. There is an ongoing study of nivolumab in first line locally advanced or metastatic urothelial carcinoma (mUC) patients.\nNKTR-214 is designed to bind to specific immune system T-cells to activate them and cause them to multiply, creating an immune response against the tumour.\nThe study will evaluate effectiveness, safety, and tolerability of NKTR-214 when combined with nivolumab in previously untreated patients with mUC and who are ineligible for cisplatin treatment.\nThere are three periods to the study: Screening, Treatment, and Follow-up. Participants will receive NKTR-214 and nivolumab by intravenous (IV) infusion every three weeks. \nThis study will recruit approximately 205 patients with mUC. Patients may receive study drugs for up to 2 years, and may participate in the study for up to 5 years.\nDuring the study, the treatments will be given, and patients will undergo blood tests, physical examinations, questionnaires, CT/MRI scans, ECG (electrocardiogram) and echocardiogram/MUGA.\nThe study, funded by Nektar Therapeutics, will involve approximately 160 centres in North/South America, Europe, and Asia/Pacific.
Summary of Results
This study was carried out by Nektar Therapeutics in order to evaluate the safety and efficacy of their study drug bempegaldesleukin (NKTR‐214) in combination with nivolumab, in patients with locally advanced or metastatic urothelial carcinoma. The study took place at 69 research centres globally, with a total of 190 patients, both male and female aged 18 years of age and over took part in the study. In this study, patients were treated with NKTR‐214 (0.006 mg/kg dose) and nivolumab (360 mg) every 3 weeks until disease progression, death, unacceptable toxicity, symptomatic deterioration, investigator or patient decision, withdrawal of consent, loss to follow‐up, sponsor decision to terminate the study, or for a maximum of 2 years from Cycle 1 Day 1. Treatment could continue beyond progression if the patient was receiving clinical benefit as determined by the Investigator. In terms of efficacy, the results of the study did not meet the study hypothesis; an objective response rate (ORR) of 17.9% (22 of 123 patients) was observed in patients whose tumours had low PD‐L1 expression. A total of 7 (5.7%) and 15 (12.2%) patients achieved complete or partial response, respectively; for these patients, the median duration of response was 13.4 months. On this study, NKTR‐214 and nivolumab were administered for up to 2 years. In terms of tolerability, the median overall duration of NKTR‐214 and nivolumab was 106.0 and 111.5 days, respectively; approximately 33% of patients received less than 6 months of treatment of NKTR‐214 and nivolumab (33.5% and 35.6%, respectively). Safety results were generally consistent for both the low PD‐L1 and high PD‐L1 populations. In conclusion, in this Phase 2 study, treatment with the combination of NKTR‐214 and nivolumab for patients with cisplatin‐ineligible, previously untreated, locally advanced or metastatic urothelial cell carcinoma resulted in: An ORR of 17.9% (95% CI = 11.6, 25.8) for patients with low PD‐L1 expression (the primary efficacy endpoint); the lower limit of the 95% confidence interval (11.6%) fell below the predefined threshold (21%). A complete response rate of 5.7% and a partial response of 12.2% (7 and 15 patients, respectively); for these patients, the median duration of response was 13.4 months. and Most patients reported at least 1 treatment‐emergent AE (TEAE; 99.5%) and Grade ≥ 3 TEA (66.0%). TEAEs leading to death were reported in 7.4% of patients
REC name
London - Hampstead Research Ethics Committee
REC reference
19/LO/0855
Date of REC Opinion
29 May 2019
REC opinion
Further Information Favourable Opinion