Study AALL07P41 Results
Asparaginase activity
ASPARLAS® demonstrated asparaginase activity data in an open-label study conducted to evaluate the PK, PD, safety, immunogenicity, and efficacy of ASPARLAS® vs ONCASPAR® as part of an augmented BFM therapy regimen:1
Efficacy data
- 100% of ASPARLAS® patients vs 95.3% of ONCASPAR® patients had PAA ≥0.1 IU/mL through 18 days following induction dose
- 92.9% of ASPARLAS® patients vs 29.5% of ONCASPAR® patients had PAA ≥0.1 IU/mL by 25 days following induction dose
This study used an off-label population. ASPARLAS® is only indicated in patients between the ages of 1 and 21 years.
The determination of efficacy was based on a demonstration of the achievement and maintenance of NPAA or NSAA ≥ 0.1 IU/mL using ASPARLAS® 2500 IU/m2 IV (assuming a 1:1 asparaginase activity relationship between these two matrices). The therapeutic threshold of asparaginase activity (≥0.1 IU/mL) either after a single dose or at ASPARLAS® steady state is considered to be associated with complete asparagine depletion based on in vitro data and clinical studies.1
Asparaginase depletion
Pharmacodynamics‡
ASPARLAS® pharmacodynamic response is related to a sustained L-asparagine depletion1
Asparagine concentrations in plasma (N=41) in patients (1 to 26 years) were maintained below the assay limit of quantification for >18 days following a single dose of ASPARLAS® 2,500 IU/m2 during the induction phase in Study AALL07P4.1
Mean CSF asparagine concentrations over time after a single dose of ASPARLAS® 2,500 IU/m2 during the induction phase1
This study used an off-label population. ASPARLAS® is only indicated in patients between the ages of 1 and 21 years.
aBFM: augmented Berlin-Frankfurt-Münster; AE: adverse event; ALL: acute lymphoblastic leukemia; ALP: alkaline phosphatase; ALT: alanine aminotransferase; aPTT: activated partial thromboplastin time; AST: aspartate aminotransferase; BFM: Berlin-Frankfurt-Munster; BSA: body surface area; CSF: cerebrospinal fluid; CTCAE: Common Terminology Criteria for Adverse Events; DFCI: Dana-Farber Cancer Institute; IM: intramuscular; IV: intravenous; NCCN: National Comprehensive Cancer Network®; NPAA: nadir plasma arparaginase activity; NSAA: nadir serum asparaginase activity; NSAID: non-steroidal anti-inflammatory drug; PD: pharmacodynamics; PK: pharmacokinetics; TDM: therapeutic drug monitoring.
* Comparative clinical significance has not been established.
† Fictitious cases. May not be representative of all patients.
‡ Clinical significance has not been established.
References:
- ASPARLAS® Product Monograph. Servier Canada.
- Data on file. Servier Canada.
- ONCASPAR® Product Monograph. Servier Canada.
- RYLAZE™ Product Monograph. Jazz Pharmaceuticals Canada Inc.
- Government of Canada. Summary Basis of Decision for Asparlas. Available at https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1718207489396.
- Government of Canada. ONCASPAR_CPID Redacted.
- Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J. 2017;7(6):e577.
- Mank V, Azhar W, Brown K. Leukocytosis. In: StatPearls. Treasure Island (FL): StatPearls Publishing; April 21, 2024.
- National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Acute Lymphoblastic Leukemia, version 4.2023 – February 05, 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.
- National Institutes of Health. National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE): Version 4.0. Available at: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5×11.pdf. Accessed December 11, 2024.
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