A Single-Arm Study of Bempegaldesleukin (NKTR-214) Plus Nivolumab in Cisplatin Ineligible Patients Who Have Locally Advanced or Metastatic Urothelial Cancer (PIVOT-10)
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| ClinicalTrials.gov Identifier: NCT03785925 |
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Recruitment Status :
Completed
First Posted : December 24, 2018
Results First Posted : March 28, 2023
Last Update Posted : March 28, 2023
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Urinary Bladder Neoplasm Neoplasm Metastasis | Biological: Bempegaldesleukin Biological: Nivolumab | Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 192 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official 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 |
| Actual Study Start Date : | April 29, 2019 |
| Actual Primary Completion Date : | February 9, 2022 |
| Actual Study Completion Date : | June 30, 2022 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Combination of bempegaldesleukin (NKTR-214) + nivolumab
Participants will receive bempegaldesleukin (NKTR-214) in combination with nivolumab.
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Biological: Bempegaldesleukin
Specified dose on specified days
Other Names:
Biological: Nivolumab Specified dose on specified days
Other Names:
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- 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 [ Time Frame: 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 ]
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.
- Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients [ Time Frame: 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. ]
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.
- 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 [ Time Frame: 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. ]
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.
- 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 [ Time Frame: 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. ]
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.
- 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 [ Time Frame: 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. ]
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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03785925
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| Study Director: | Study Director | Nektar Therapeutics |
Documents provided by Nektar Therapeutics:
| Responsible Party: | Nektar Therapeutics |
| ClinicalTrials.gov Identifier: | NCT03785925 |
| Other Study ID Numbers: |
18-214-10 CA045-012 ( Other Identifier: Bristol-Myers Squibb Protocol ID ) 2018-003636-79 ( EudraCT Number ) |
| First Posted: | December 24, 2018 Key Record Dates |
| Results First Posted: | March 28, 2023 |
| Last Update Posted: | March 28, 2023 |
| Last Verified: | March 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Bladder Bladder Cancer CD122 Cisplatin Ineligible Immuno-oncology Immunotherapy Locally Advanced Urothelial Cancer Metastatic Urothelial Cancer mUC Natural Killer Cells Nivolumab |
NKTR-214 Opdivo® PD-L1 Urothelial Cancer Urothelial Metastatic Urothelial Carcinoma Urothelial Carcinoma Bempegaldesleukin BEMPEG CPI Combination IL-2 |
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Neoplasms Neoplasm Metastasis Urinary Bladder Neoplasms Neoplastic Processes Pathologic Processes 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 Nivolumab Antineoplastic Agents, Immunological Antineoplastic Agents Immune Checkpoint Inhibitors Molecular Mechanisms of Pharmacological Action |