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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)

Primary Purpose

Ependymoma, Ewing Sarcoma, High-grade Glioma

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Nivolumab

NKTR-214

About this trial

This is an interventional treatment trial for Ependymoma focused on measuring 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

Eligibility Criteria

undefined - 30 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm Type

Experimental

Arm Label

A1W Dosing schema

A1F Dosing schema

A2W Dosing schema

A2F Dosing schema

Part B: Cohort B1 Neuroblastoma

Part B: Cohort B2 Ewing sarcoma

Part B: Cohort B3 Rhabdomyosarcoma

Part B: Cohort B4 Miscellaneous solid tumors

Part B: Cohort B5 NHL/leukemia

Part B: Cohort B6 High-grade glioma

Part B: Cohort B7 Medulloblastoma and Embryonal Tumors

Part B: Cohort B8 Ependymoma

Part B: Cohort B9 Miscellaneous brain tumors

Arm Description

Outcomes

Primary Outcome Measures

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).

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.

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.

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.

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.

Number of Participants Who Died - Part A

Number of participants who died.

Maximum Observed Plasma Concentration (Cmax) - Part A

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

Trough Observed Concentration (Ctrough) - Part A

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

Area Under the Plasma Concentration (AUC) - Part A

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

Secondary Outcome Measures

Full Information

NCT ID

NCT04730349

First Posted

January 26, 2021

Last Updated

March 22, 2023

Sponsor

Bristol-Myers Squibb

Collaborators

Nektar Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT04730349

Brief Title

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

Acronym

PIVOT IO 020

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)

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

Business objectives have changed

Study Start Date

June 3, 2021 (Actual)

Primary Completion Date

June 22, 2022 (Actual)

Study Completion Date

June 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bristol-Myers Squibb

Collaborators

Nektar Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ependymoma, Ewing Sarcoma, High-grade Glioma, Leukemia and Lymphoma, Medulloblastoma, Miscellaneous Brain Tumors, Miscellaneous Solid Tumors, Neuroblastoma, Relapsed, Refractory Malignant Neoplasms, Rhabdomyosarcoma

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, NIVO, Non-rhabdomyosarcoma soft-tissue sarcomas, Opdivo®, Pediatric cancer, Pediatric malignancy, Rhabdomyosarcoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Sequential Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

A1W Dosing schema

Arm Type

Experimental

Arm Title

A1F Dosing schema

Arm Type

Experimental

Arm Title

A2W Dosing schema

Arm Type

Experimental

Arm Title

A2F Dosing schema

Arm Type

Experimental

Arm Title

Part B: Cohort B1 Neuroblastoma

Arm Type

Experimental

Arm Title

Part B: Cohort B2 Ewing sarcoma

Arm Type

Experimental

Arm Title

Part B: Cohort B3 Rhabdomyosarcoma

Arm Type

Experimental

Arm Title

Part B: Cohort B4 Miscellaneous solid tumors

Arm Type

Experimental

Arm Title

Part B: Cohort B5 NHL/leukemia

Arm Type

Experimental

Arm Title

Part B: Cohort B6 High-grade glioma

Arm Type

Experimental

Arm Title

Part B: Cohort B7 Medulloblastoma and Embryonal Tumors

Arm Type

Experimental

Arm Title

Part B: Cohort B8 Ependymoma

Arm Type

Experimental

Arm Title

Part B: Cohort B9 Miscellaneous brain tumors

Arm Type

Experimental

Intervention Type

Biological

Intervention Name(s)

Nivolumab

Other Intervention Name(s)

BMS-936558-01

Intervention Description

Specified dose on specified days

Intervention Type

Biological

Intervention Name(s)

NKTR-214

Other Intervention Name(s)

Bempegaldesleukin (BEMPEG)

Intervention Description

Specified dose on specified days

Primary Outcome Measure Information:

Title

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

Description

Time Frame

From first dose to 42 days after first dose

Title

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

Description

Time Frame