A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination With Nivolumab in Children, Adolescents and Young Adults With Recurrent or Treatment-resistant Cancer (PIVOT IO 020)
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| ClinicalTrials.gov Identifier: NCT04730349 |
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Recruitment Status :
Terminated
(Business objectives have changed)
First Posted : January 29, 2021
Results First Posted : March 24, 2023
Last Update Posted : March 24, 2023
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Sponsor:
Bristol-Myers Squibb
Collaborator:
Nektar Therapeutics
Information provided by (Responsible Party):
Bristol-Myers Squibb
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Brief Summary:
The purpose of this study is to first, in Part A, assess the safety, tolerability and drug levels of Bempegaldesleukin (BEMPEG) in combination with nivolumab and then, in Part B, to estimate the preliminary efficacy in children, adolescents and young adults with recurrent or treatment-resistant cancer.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Ependymoma Ewing Sarcoma High-grade Glioma Leukemia and Lymphoma Medulloblastoma Miscellaneous Brain Tumors Miscellaneous Solid Tumors Neuroblastoma Relapsed, Refractory Malignant Neoplasms Rhabdomyosarcoma | Biological: Nivolumab Biological: NKTR-214 | Phase 1 Phase 2 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 15 participants |
| Allocation: | Non-Randomized |
| Intervention Model: | Sequential Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase 1/2 Study of Bempegaldesleukin in Combination With Nivolumab in Children, Adolescents, and Young Adults With Recurrent or Refractory Malignancies (PIVOT IO 020) |
| Actual Study Start Date : | June 3, 2021 |
| Actual Primary Completion Date : | June 22, 2022 |
| Actual Study Completion Date : | June 22, 2022 |
Resource links provided by the National Library of Medicine
Drug Information available for:
Nivolumab
| Arm | Intervention/treatment |
|---|---|
| Experimental: A1W Dosing schema |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: A1F Dosing schema |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: A2W Dosing schema |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: A2F Dosing schema |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B1 Neuroblastoma |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B2 Ewing sarcoma |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B3 Rhabdomyosarcoma |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B4 Miscellaneous solid tumors |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B5 NHL/leukemia |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B6 High-grade glioma |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B7 Medulloblastoma and Embryonal Tumors |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B8 Ependymoma |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
| Experimental: Part B: Cohort B9 Miscellaneous brain tumors |
Biological: Nivolumab
Specified dose on specified days
Other Name: BMS-936558-01 Biological: NKTR-214 Specified dose on specified days
Other Name: Bempegaldesleukin (BEMPEG) |
Primary Outcome Measures :
- Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A [ Time Frame: From first dose to 42 days after first dose ]Number of participants with dose-limiting toxicities (DLTs). DLTs were collected and evaluated for Part A within the DLT evaluation period, which started on Cycle 1 Day 1 (first dose) and ended at Day 42 (42 days after first dose of the study therapy).
- Number of Participants With Adverse Events (AEs) - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Number of participants with adverse events (AEs). An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
- Number of Participants With Serious Adverse Events (SAEs) - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Number of participants with serious adverse events (SAEs). SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an important medical event.
- Number of Participants With Drug-Related Adverse Events - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Number of participants with drug-related adverse events. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
- Number of Participants With Adverse Events Leading to Discontinuation - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Number of participants with adverse events leading to discontinuation. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment.
- Number of Participants Who Died - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Number of participants who died.
- Maximum Observed Plasma Concentration (Cmax) - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
- Trough Observed Concentration (Ctrough) - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
- Area Under the Plasma Concentration (AUC) - Part A [ Time Frame: From first dose to 30 days after last dose (up to approximately 6 months) ]Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.
Information from the National Library of Medicine
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| Ages Eligible for Study: | up to 30 Years (Child, Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Age < 18 years for Part A and Part B
- Age up to 30 years for Part B Cohorts B2, B3 and B4
- Must have received standard of care therapy and there must be no potentially curative treatment available
- Histologically confirmed with malignant neoplasms that are refractory, relapsed, or curative treatments are lacking
- Must have measurable or evaluable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for solid tumors, Response Assessment in Neuro-Oncology (RANO) or Response Assessment in Pediatric Neuro-Oncology (RAPNO) for central nervous system tumors, International Pediatric Non-Hodgkin Lymphoma Response Criteria for non-Hodgkin lymphoma (NHL), revised International Neuroblastoma Response Criteria (INRC) for neuroblastoma, modified National Comprehensive Cancer Network (NCCN) Criteria for acute lymphoblastic leukemia, and modified Cheson et al International Working Group criteria for acute myeloid leukemia
- Lansky play score for age ≤ 16 years or Karnofsky performance score for age > 16 years assessed within 2 weeks of enrollment must be ≥ 60
Exclusion Criteria:
- Osteosarcoma, T-cell/Natural Killer (NK) cell leukemia/lymphoma, and Hodgkin's lymphoma
- Need for > 2 antihypertensive medications for management of hypertension (including diuretics)
- Known cardiovascular history, including unstable or deteriorating cardiac disease, within the previous 12 months prior to screening
- Inadequately treated adrenal insufficiency
- Active, known, or suspected autoimmune disease
- Active infection requiring systemic therapy within 14 days prior to first dose
- Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of start of study treatment
- Prior allogeneic stem cell transplant
- Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection either suspected or confirmed within 4 weeks prior to screening
Other protocol-defined inclusion/exclusion criteria apply
Information from the National Library of Medicine
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): NCT04730349
Locations
Show 18 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Nektar Therapeutics
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Study Documents (Full-Text)
Documents provided by Bristol-Myers Squibb:
Documents provided by Bristol-Myers Squibb:
Study Protocol and Statistical Analysis Plan [PDF] November 28, 2021
Additional Information:
| Responsible Party: | Bristol-Myers Squibb |
| ClinicalTrials.gov Identifier: | NCT04730349 |
| Other Study ID Numbers: |
CA045-020 2020-000854-85 ( EudraCT Number ) |
| First Posted: | January 29, 2021 Key Record Dates |
| Results First Posted: | March 24, 2023 |
| Last Update Posted: | March 24, 2023 |
| Last Verified: | March 2023 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Bristol-Myers Squibb:
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B-cell leukemia/lymphoma/non-Hodgkin lymphoma (NHL) BEMPEG Bempegaldesleukin CD122-Biased Agonist CD122-Biased Cytokine Check point inhibitor Ependymoma Ewing sarcoma High-grade glioma (HGG)/diffuse intrinsic pontine glioma (DIPG) Immunotherapy IL-2 IL-2 Receptor Agonist Leukemia and lymphoma |
Medulloblastoma Melanoma Miscellaneous brain tumors Miscellaneous solid tumors Neuroblastoma Nivolumab NKTR-214 NIVO Non-rhabdomyosarcoma soft-tissue sarcomas Opdivo® Pediatric cancer Pediatric malignancy Rhabdomyosarcoma |
Additional relevant MeSH terms:
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Lymphoma Neoplasms Leukemia Sarcoma Glioma Brain Neoplasms Neuroblastoma Rhabdomyosarcoma Ependymoma Sarcoma, Ewing Medulloblastoma Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders |
Immune System Diseases Neoplasms, Connective and Soft Tissue Neoplasms, Neuroepithelial Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms, Glandular and Epithelial Neoplasms, Nerve Tissue Central Nervous System Neoplasms Nervous System Neoplasms Neoplasms by Site Brain Diseases Central Nervous System Diseases Nervous System Diseases Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive |