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)

Bristol-Myers Squibb (BMS)

Status and phase: Terminated; Phase 2; Phase 1

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

Treatments: Biological: Nivolumab; Biological: NKTR-214

Study type: Interventional

Funder types: Industry

Identifiers

NCT04730349

CA045-020

2020-000854-85 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: Under 30 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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15 participants in 13 patient groups

A1W Dosing schema

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

A1F Dosing schema

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

A2W Dosing schema

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

A2F Dosing schema

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B1 Neuroblastoma

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B2 Ewing sarcoma

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B3 Rhabdomyosarcoma

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B4 Miscellaneous solid tumors

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B5 NHL/leukemia

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B6 High-grade glioma

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B7 Medulloblastoma and Embryonal Tumors

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B8 Ependymoma

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab

Part B: Cohort B9 Miscellaneous brain tumors

Experimental group

Treatment:

Biological: NKTR-214

Biological: Nivolumab