This is a open label Phase 1 study to evaluate the safety, tolerability, and pharmacokinetics of escalating oral doses of NLG802, an investigational agent intended to inhibit the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme, in combination with temozolomide chemotherapy in children with primary brain tumors.
The study will enroll subjects 5 to 21 years of age with relapsed or refractory primary brain or spinal malignancy of any histology, who have exhausted available curative treatment options. A standard 3+3 dose-escalation design will be used to determine the pediatric maximum tolerated dose (MTD) for NLG802 indoximod prodrug in combination with temozolomide (Treatment Regimen). The MTD of NLG802 for the Treatment Regimen will be the highest dose level where no more than 1 of 6 subjects have (a) Regimen-Limiting Toxicity(/ies) (RLT\[s\]) in Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2. Toxicity will be defined and graded using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. All subjects will have timed blood draws for NLG802 pharmacokinetic (PK) analysis in Cycle 1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
NLG802 will be taken by mouth twice daily, throughout each treatment cycle.
Temozolomide will be taken by mouth once daily, on days 1-5 of each treatment cycle.
Augusta University, Georgia Cancer Center
Augusta, Georgia, United States
Maximum tolerated dose in pediatric participants for NLG802 in combination with temozolomide.
Determined by number of patients with dose limiting toxicities.
Time frame: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.
Incidence of Regimen-limiting toxicities in in pediatric participants for NLG802 in combination with temozolomide.
Determined by number of patients with regimen limiting toxicities.
Time frame: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.
Pharmacokinetics in pediatric participants for NLG802 in combination with temozolomide
Serum concentrations (Cmax/Steady State).
Time frame: Cycle 1, which will be 28 days duration plus any toxicity-related delay before starting Cycle 2.
Overall survival for NLG802 in combination with temozolomide.
Time frame: Day 1 up to 12 months.
Evidence of efficacy for NLG802 in combination with temozolomide based on change to objective response rate.
Measured by subjects who achieve complete response, partial response or no response.
Time frame: Day 1 up to 12 months.
Percentage of patients with adverse events
Assessment of safety and tolerability of NLG802 in combination with temozolomide.
Time frame: Day 1 up to 12 months.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.