Pharmacokinetics and Pharmacodynamics Profile
Pharmacokinetics (PK) profile1*
ONCASPAR®’s mean elimination half-life was approximately 5.3 days following a single IV infusion.1*
In Study DFCI 11-001, assessments of asparaginase activity were performed following a single IV dose of ONCASPAR® 2,500 U/m2 BSA during Induction, and every two weeks during post-Induction.1*
Plasma asparaginase activity in PK study
During Induction, plasma asparaginase activity ≥0.1 U/mL was sustained in 93.5% of subjects 18 days after administration.
During the post-Induction phase, a nadir (trough) asparaginase activity above 0.4 U/mL was sustained in 100% of evaluable subjects from Week 7 up until Week 25 (i.e., N=86 on Week 7, N=84 on Week 13, and N=78 on Weeks 19 and 25).
Adapted from the ONCASPAR® Product Monograph.
These results indicate that, when ONCASPAR® 2,500 U/m2 BSA is administered every two weeks, clinically relevant asparaginase activity is sustained over the entire dosing interval (i.e., two weeks).1*
Pharmacodynamics (PD) profile1*
The anti-leukemic effect of L-asparaginase is related to a sustained L-asparagine depletion in blood and cerebrospinal fluid (CSF).1†
In Study AALL07P4, the PD effect of ONCASPAR® was assessed after IV administration:
ONCASPAR® was assessed in 47 evaluable subjects with high-risk B-precursor ALL who received IV doses of ONCASPAR® 2,500 U/m2 BSA during the Induction and Consolidation phases.
L-asparagine depletion in blood
Plasma L-asparagine concentrations were depleted to below the assay limit of quantification within 24 hours following the Induction and first Consolidation dose of ONCASPAR®. Depletion was sustained for approximately two weeks.
L-asparagine depletion in CSF:
- In addition, CSF asparagine concentrations were reduced by the 4th day following the Induction dose, and remained largely undetectable until the 25th day after dosing.
aBFM: augmented Berlin-Frankfurt-Münster; ALL: acute lymphoblastic leukemia; BSA: body surface area; CNS: central nervous system; CSF: cerebrospinal fluid; DFCI: Dana-Farber Cancer Institute; ELISA: enzyme-linked immunosorbent assay; IM: intramuscular; IV: intravenous; PD: pharmacodynamics; PK: pharmacokinetics; NCCN: National Comprehensive Cancer Network®; TDM: therapeutic drug monitoring.
* Clinical significance has not been established.
† Comparative clinical significance has not been established.
‡ Fictitious cases. May not be representative of all patients.
§ Native E. coli L-asparaginase is not available in Canada.
References:
- ONCASPAR® Product Monograph. Servier Canada. August 20, 2024.
- ONCASPAR_CPID Redacted.
- ASPARLAS® Product Monograph. Servier Canada. March 8, 2024.
- RYLAZE™ Product Monograph. Jazz Pharmaceuticals Canada Inc.
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.2.2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/all.pdf. Accessed November 8, 2024.
- Vrooman LM et al. Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: Results of DFCI 11-001. J Clin Oncol. 2021;39(31):3496–3505.
