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EpendymomaPhase 1/2PIVOT IO 020NCT04730349

A Study of Bempegaldesleukin (BEMPEG: NKTR-214) in Combination With Nivolumab in Children, Adolescents and Young Adults With Recurrent or Treatment-resistant Cancer

A Phase 1/2 study testing Nivolumab and NKTR-214 in people with Ependymoma and Ewing Sarcoma, run by Bristol-Myers Squibb at 18 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 30 years
Conditions the study is for
Ependymoma, Ewing Sarcoma, High-grade Glioma
What is being tested?
Nivolumab and NKTR-214
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
18 sitesin 6 countries
Study dates
3 Jun 2021to 22 Jun 2022
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

18 sites in 6 countries.

18 sites in 6 countries

Australia4 sites
  • Local Institution - 0002

    Parkville, Victoria, 3052

  • Local Institution - 0003

    Perth, Western Australia, 6009

  • Local Institution - 0001

    Randwick, New South Wales, 2031

  • Local Institution

    South Brisbane, Queensland, 4101

Other trials in Australia

France4 sites
  • Local Institution - 0014

    Lyon, 69373 cedex 03

  • Local Institution - 0016

    Marseille, 13385

  • Local Institution - 0015

    Paris, 75005

  • Local Institution - 0013

    Villejuif, Val-de-Marne, 94805

Other trials in France

Spain4 sites
  • Local Institution - 0008

    Barcelona, 08035

  • Local Institution - 0009

    Madrid, Madrid, Comunidad de, 28009

  • Local Institution - 0059

    Seville, 41013

  • Local Institution - 0028

    Valencia, 46026

Other trials in Spain

Germany3 sites
  • Local Institution - 0038

    Hamburg, 20246

  • Local Institution - 0039

    Tübingen, 72076

  • Local Institution - 0037

    Würzburg, 97080

Other trials in Germany

United States2 sites
  • Local Institution - 0029

    Little Rock, Arkansas, 72202

  • Local Institution - 0011

    St Louis, Missouri, 63110

Other trials in United States

Italy1 site
  • Local Institution - 0027

    Milan, 20133

Other trials in Italy

About this study

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)

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.

Being tested
Nivolumab, NKTR-214
Keywords
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
Medical subject headings
Ependymoma, Sarcoma, Ewing, Glioma, Leukemia, Lymphoma, Medulloblastoma, Neuroblastoma, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NivolumabBiological

    Also called BMS-936558-01

    Specified dose on specified days

  • NKTR-214Biological

    Also called Bempegaldesleukin (BEMPEG)

    Specified dose on specified days

Study groups in NCT04730349
Study groupRoleWhat they receive
A1W Dosing schemaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
A1F Dosing schemaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
A2W Dosing schemaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
A2F Dosing schemaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B1 NeuroblastomaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B2 Ewing sarcomaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B3 RhabdomyosarcomaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B4 Miscellaneous solid tumorsExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B5 NHL/leukemiaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B6 High-grade gliomaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B7 Medulloblastoma and Embryonal TumorsExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B8 EpendymomaExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214
Part B: Cohort B9 Miscellaneous brain tumorsExperimentalNot described
Receives: Biological: Nivolumab; Biological: NKTR-214

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A

    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).

    Measured: From first dose to 42 days after first dose

  2. Number of Participants With Adverse Events (AEs) - Part A

    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.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  3. Number of Participants With Serious Adverse Events (SAEs) - Part A

    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.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  4. Number of Participants With Drug-Related Adverse Events - Part A

    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.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  5. Number of Participants With Adverse Events Leading to Discontinuation - Part A

    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.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  6. Number of Participants Who Died - Part A

    Number of participants who died.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  7. Maximum Observed Plasma Concentration (Cmax) - Part A

    Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  8. Trough Observed Concentration (Ctrough) - Part A

    Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

  9. Area Under the Plasma Concentration (AUC) - Part A

    Pharmacokinetics (PK) of bempegaldesleukin and nivolumab derived from serum concentration versus time data.

    Measured: From first dose to 30 days after last dose (up to approximately 6 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2021
  2. Study start3 Jun 2021
  3. Primary completion22 Jun 2022
  4. Study completion22 Jun 2022

Why it stopped: Business objectives have changed

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04730349
Sponsor's protocol ID
CA045-020
Other IDs
2020-000854-85
Acronym
PIVOT IO 020
Status last verified
Mar 2023
First submitted
26 Jan 2021
Last updated
24 Mar 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nivolumab and NKTR-214 in people with Ependymoma and Ewing Sarcoma, run by Bristol-Myers Squibb at 18 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Australia, France, Spain, Germany, United States and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 Mar 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Dose-Limiting Toxicities (DLTs) - Part A (time frame: From first dose to 42 days after first dose). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2023.

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