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NCT03785925: PIVOT-10

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

Completed Phase 2 Results posted Last updated 28 March 2023
What this trial tests

Phase 2 trial testing Bempegaldesleukin in Urinary Bladder Neoplasm in 192 participants. Completed in 30 June 2022.

Timeline
29 April 2019
Primary endpoint
9 February 2022
30 June 2022

Quick facts

Lead sponsorNektar Therapeutics
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment192
Start date29 April 2019
Primary completion9 February 2022
Estimated completion30 June 2022
Sites70 locations across France, Italy, Finland, Netherlands, Greece, Russia, Belgium, United Kingdom

Drugs / interventions tested

Conditions studied

Sponsor

Nektar Therapeutics — full company profile →

Who can join

18 and older, any sex, with Urinary Bladder Neoplasm or Neoplasm Metastasis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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 Primary · 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

GroupValue95% CI
PD-L1 Low22
Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Per Blinded Independent Central Review (BICR) in All Treated Patients Secondary · 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 shor

GroupValue95% CI
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab37
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 Secondary · 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

GroupValue95% CI
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (All Treated Population)13.48.2 – NA
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (PD-L1 Low Population)13.46.2 – NA
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 Secondary · 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.

GroupValue95% CI
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (All Treated Population)36
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (PD-L1 Low Population)20
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 Secondary · 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 cens

GroupValue95% CI
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (All Treated Population)15.910.7 – NA
Combination of Bempegaldesleukin (NKTR-214) + Nivolumab (PD-L1 Low Population)14.38.2 – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs were reported from the time of first study drug(s) administration until 100 days after the last dose of all study drug(s), up to a maximum of approximately 27 months.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Combination of Bempegaldesleukin (NKTR-214) + Nivolumab
Serious: 98/188 (52%)
Deaths: 127/188

Serious adverse events (99 terms)

ReactionSystemCombination of Bempegaldes…
Urinary tract infectionInfections and infestations
Acute kidney injuryRenal and urinary disorders
HaematuriaRenal and urinary disorders
DiarrhoeaGastrointestinal disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
UrosepsisInfections and infestations
Corona virus infectionInfections and infestations
FatigueGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Urinary tract infection enterococcalInfections and infestations
HydronephrosisRenal and urinary disorders
NephritisRenal and urinary disorders
VomitingGastrointestinal disorders
General physical health deteriorationGeneral disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Atrial fibrillationCardiac disorders
Cardiac failureCardiac disorders
MyocarditisCardiac disorders
Deep vein thrombosisVascular disorders
HypotensionVascular disorders
Peripheral ischaemiaVascular disorders
DehydrationMetabolism and nutrition disorders
Cerebrovascular accidentNervous system disorders
Other adverse events (48 terms — click to expand)

ReactionSystemCombination of Bempegaldes…
PyrexiaGeneral disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
AnaemiaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
NauseaGastrointestinal disorders
ConstipationGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Pruritus generalisedSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
AstheniaGeneral disorders
VomitingGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Oedema peripheralGeneral disorders
HaematuriaRenal and urinary disorders
HypothyroidismEndocrine disorders
ChillsGeneral disorders
EosinophiliaBlood and lymphatic system disorders
Blood creatinine increasedInvestigations
Influenza like illnessGeneral disorders
Back painMusculoskeletal and connective tissue disorders
DizzinessNervous system disorders
HypotensionVascular disorders
CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HeadacheNervous system disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
HyperthyroidismEndocrine disorders
Abdominal painGastrointestinal disorders
Rash generalisedSkin and subcutaneous tissue disorders
Gamma-glutamyltransferase increasedInvestigations
InsomniaPsychiatric disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Weight decreasedInvestigations
Dry skinSkin and subcutaneous tissue disorders
Musculoskeletal painMusculoskeletal and connective tissue disorders
HyponatraemiaMetabolism and nutrition disorders
MyalgiaMusculoskeletal and connective tissue disorders
Blood alkaline phosphatase increasedInvestigations

Most-reported serious reactions: Urinary tract infection, Acute kidney injury, Haematuria, Diarrhoea, Pyrexia, Pneumonia, Urosepsis, Corona virus infection.

Data from ClinicalTrials.gov NCT03785925 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Enhancing cancer immunotherapy with nanomedicine.
    Irvine DJ, Dane EL. · · 2020 · cited 569× · PMID 32005979 · DOI 10.1038/s41577-019-0269-6
  2. Targeting cytokine and chemokine signaling pathways for cancer therapy.
    Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
  3. Immunomodulatory Effects of IL-2 and IL-15; Implications for Cancer Immunotherapy.
    Yang Y, Lundqvist A. · · 2020 · cited 149× · PMID 33266177 · DOI 10.3390/cancers12123586
  4. A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases.
    Raeber ME, Sahin D, Karakus U, Boyman O. · · 2023 · cited 139× · PMID 37004361 · DOI 10.1016/j.ebiom.2023.104539
  5. Effects of interleukin-2 in immunostimulation and immunosuppression.
    Pol JG, Caudana P, Paillet J, Piaggio E, et al · · 2020 · cited 132× · PMID 31611250 · DOI 10.1084/jem.20191247
  6. Current Strategies and Novel Therapeutic Approaches for Metastatic Urothelial Carcinoma.
    Mollica V, Rizzo A, Montironi R, Cheng L, et al · · 2020 · cited 75× · PMID 32498352 · DOI 10.3390/cancers12061449
  7. The application of Interleukin-2 family cytokines in tumor immunotherapy research.
    Zhou Y, Quan G, Liu Y, Shi N, et al · · 2023 · cited 32× · PMID 36936961 · DOI 10.3389/fimmu.2023.1090311
  8. Emerging therapeutic agents for genitourinary cancers.
    Zarrabi K, Paroya A, Wu S. · · 2019 · cited 31× · PMID 31484560 · DOI 10.1186/s13045-019-0780-z

Verify or expand the search:

Other trials of Bempegaldesleukin

Trials testing the same drug.

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Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03785925.

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