A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer

Study Overview
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Brief Summary
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The main purpose of this study is to evaluate the anti-tumor activity of bempegaldesleukin (NKTR-214) in combination with nivolumab by assessing the objective response rate (ORR) in cisplatin ineligible, locally advanced or metastatic urothelial cancer patients.

Official Title
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A Phase 2, Single-Arm Study of Bempegaldesleukin (NKTR-214) in Combination With Nivolumab in Cisplatin Ineligible, Locally Advanced or Metastatic Urothelial Cancer Patients

Conditions
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Urinary Bladder Neoplasm, Neoplasm Metastasis

Intervention / Treatment
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* Biological: Bempegaldesleukin
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Provide written, informed consent to participate in the study and follow the study procedures Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2 Measurable disease per RECIST 1.1 criteria Histologically or cytologically documented inoperable, locally advanced or metastatic urothelial cell carcinoma (also termed TCC) Fresh biopsy or archival tissue No prior systemic chemotherapy or investigational agent for inoperable locally advanced or mUC Ineligible for cisplatin Key Exclusion Criteria: Patients who have an active, known or suspected autoimmune disease Patients must not have received prior IL-2 therapy Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2 pathway, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways Patients with hypertension must be on a stable antihypertensive regimen for the 14 days prior to Cycle 1 Day 1 Additional protocol-defined inclusion/exclusion criteria applied

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination of bempegaldesleukin (NKTR-214) + nivolumab<br>Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab. | Biological: Bempegaldesleukin<br>* Specified dose on specified days<br>* Other names: BMS-986321;Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936658;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression | To evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the ORR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in patients whose tumors have low programmed cell death ligand 1 (PD-L1) expression. ORR was defined as the percentage of patients with confirmed objective response of Complete Response (CR) or Partial Response (PR) on or before the first progressive disease and any subsequent anticancer therapy. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients | To evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the ORR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in all treated patients. ORR was defined as the percentage of patients with confirmed objective response of Complete Response (CR) or Partial Response (PR) on or before the first progressive disease and any subsequent anticancer therapy. CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) had to have reduction in short axis to <10 mm. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. | Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months. | 
| Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression | To evaluate the effect of NKTR 214 in combination with nivolumab by assessing DOR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) per blinded independent central review (BICR) in all treated patients and patients whose tumors have low PD-L1 expression. DOR is defined for patients who have a confirmed Complete Response (CR) or Partial Response (PR) as the date from first documented CR or PR per RECIST 1.1 to the date of documentation of disease progression as assessed by BICR or death due to any cause, whichever is earlier. Patients who do not have disease progression or die will be censored on the date of their last evaluable tumor assessment. | Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months. | 
| Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression | To evaluate the anti-tumor activity of NKTR-214 in combination with nivolumab by assessing the ORR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Investigator Assessment in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression. ORR was defined as the percentage of patients with confirmed objective response of Complete Response (CR) or Partial Response (PR) on or before the first progressive disease and any subsequent anticancer therapy. | Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months. | 
| Duration of Response (DOR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 by Investigator in All Treated Patients and Patients Whose Tumors Have Low Programmed Cell Death Ligand (PD-L1) Expression | To evaluate the effect of NKTR 214 in combination with nivolumab by assessing DOR by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by Investigator Assessment in all treated patients and patients whose tumors have low PD-L1 expression. DOR is defined for patients who have a confirmed Complete Response (CR) or Partial Response (PR) as the date from first documented CR or PR per RECIST 1.1 to the date of documentation of disease progression as assessed by BICR or death due to any cause, whichever is earlier. Patients who do not have disease progression or die will be censored on the date of their last evaluable tumor assessment. | Tumor assessments were performed at baseline and every 9 weeks from Cycle 1 Day 1 for the first 12 months, and then every 12 weeks as indicated in the Schedule of Events, up to approximately 27 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mUC, Bladder, Bladder Cancer, CD122, Cisplatin Ineligible, Immuno-oncology, Immunotherapy, Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer, Natural Killer Cells, Nivolumab, NKTR-214, Opdivo®, PD-L1, Urothelial Cancer, Urothelial, Metastatic Urothelial Carcinoma, Urothelial Carcinoma, Bempegaldesleukin, BEMPEG, CPI Combination, IL-2