Phase 1/2 Study of Bempegaldesleukin in Combination with Nivolumab in Children, Adolescents, and Young Adults with Recurrent or Refractory Malignancies (CA045020; PIVOT IO 020)

Study Description:

This is an open-label, sequential-arm, Phase 1b/2 clinical trial of bempegaldesleukin in combination with nivolumab in pediatric participants with malignancies that are refractory, relapsed, or participants for whom curative treatments are lacking. This is a study which will administer these two medications intravenously every 3 weeks.

Study Eligibility:

Inclusion Criteria

• Participants must have received standard of care therapy, and there must be no potentially curative treatment available.
• A histologically confirmed malignancy that is refractory, relapsed, or patients for whom curative treatments are lacking, including poor prognosis newly diagnosed high-grade glioma and diffuse intrinsic pontine glioma (DIPG).
• Participants must have measurable or evaluable disease.
• Lansky score for ages < 16 years or Karnofsky performance score for age > 16 years assessed with 2 weeks of enrollment must be > 60.
• Substantial recovery from prior therapy.
• An interval of 4 weeks or 5 half-lives of a targeted therapy, whichever is longer, after the last administration of any other treatment for malignancies (6 weeks for nitrosoureas). The interval from most recent biological agent must be 7 days or 5 half-lives, whichever is longer.
• Participants who have received high-dose chemotherapy with autologous hematopoietic cell transplantation must be at least 6 months post-hematopoietic cell transplantation and they must have a CD4 count of at least 200.
• Participants must be receiving not more than 0.05 mg/kg dexamethasone per day (or equivalent).
• Prior palliative radiotherapy must be completed at least 2 weeks prior to first dose of study drug.
• Documented left ventricular ejection fraction > 45% using standard echocardiogram or multigated acquisition scan test.

Exclusion Criteria

• Participants with osteosarcoma, T-cell/natural killer-cell leukemia/lymphoma, and Hodgkin’s lymphoma.
• Any condition including medical, emotional, psychiatric, or logistical that, in the opinion of the Investigator, would preclude the participant from adhering to the protocol or would increase the risk associated with study participation or study drug administration or interfere with the interpretation of safety results.
• Active infection requiring systemic therapy within 14 days prior to first dose.
• Need for > 2 antihypertensive medications for management of hypertension.
• Known cardiovascular history, including unstable or deteriorating cardiac disease, with previous 12 months prior to screening.
• History of pulmonary embolism deep vein thrombosis, or prior clinically significant venous or non-CVA/TIA arterial thromboembolic event within 3 months prior to treatment assignment.
• Participants with inadequately treated adrenal insufficiency.
• Participants with an active known or suspected autoimmune disease.
• Participants with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence or an external trigger are permitted enroll.
• Participants with a condition requiring systemic treatment with either corticosteroids or immunosuppressive medications within 14 days of start of study treatment. Inhaled or topical steroids and adrenal replacement steroid doses > 0.12 mg/kg daily prednisone equivalent are permitted in the absence of active autoimmune disease.
• Known human immunodeficiency virus (HIV) positive with an Acquired Immune Deficiency syndrome (AIDS) – defining opportunistic infection within last year, or a current CD4 count < 350 cells/uL.
• Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ or the prostate cervix or breast.