Asparlas (calaspargase pegol-mknl) / Servier, Takeda, Leadiant Biosci - LARVOL DELTA

Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2/3 | N=790 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | Trial completion date: Mar 2028 ➔ Sep 2028

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • BCL2

A Phase 2 Study to Evaluate Efficacy of Calaspargase Pegol-mknl and Decitabine Combined With Venetoclax in Pediatric, Adolescent, and Young Adult Patients With Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia (T-ALL) and T- Cell Lymphoblastic Lymphoma (T-LLy) (clinicaltrials.gov) - P2 | N=22 | Not yet recruiting | Sponsor: M.D. Anderson Cancer Center | Initiation date: Feb 2025 ➔ Jun 2025

Trial initiation date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

The ALL-IN Approach: Confronting ALL With a Multi-Agent Chemotherapy Regimen (ASPHO 2025) - "Discuss the clinical safety profile, adverse reaction management, and important safety information for Asparlas. This non-CME symposium is supported by Servier Pharmaceuticals."

Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Higher Rates of Hypersensitivity Reactions to Calaspargase Compared With Pegaspargase: A Single Center Retrospective Review. (PubMed, Pediatr Blood Cancer) - "The current administration of Cal-PEG in large cooperative group trials will allow for a postmarketing exploration of the true risk of HSR and associated patient-specific risk factors."

Journal • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology • Pediatrics

SPARK-ALL: Calaspargase Pegol in Adults with ALL (clinicaltrials.gov) - P2/3 | N=122 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial completion date: Feb 2027 ➔ Feb 2026 | Trial primary completion date: Feb 2027 ➔ Feb 2026 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Venetoclax Basket Trial for High Risk Hematologic Malignancies (clinicaltrials.gov) - P1 | N=92 | Recruiting | Sponsor: Andrew E. Place, MD | Trial completion date: Apr 2027 ➔ Jul 2028 | Trial primary completion date: Apr 2025 ➔ Jul 2026

Pan tumor • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • ABL1 • BCL2 • BCR • FLT3 • IKZF1 • KMT2A

A 12-Step Desensitization Protocol for Calaspargase Pegol-mknl. (PubMed, J Pediatr Pharmacol Ther) - "Asparaginase Erwinia chrysanthemi (recombinant)-rywn (recombinant Erwinia) is an alternative for those with HSRs to pegaspargase. Here, we describe an 11-year-old boy with relapsed ALL who developed HSRs to both pegaspargase and recombinant Erwinia. This is the report of a novel desensitization protocol for calaspargase pegol-mknl (calaspargase) with no adverse events and adequate serum asparaginase activity."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology

Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia (clinicaltrials.gov) - P2 | N=171 | Not yet recruiting | Sponsor: National Cancer Institute (NCI) | Initiation date: Jan 2025 ➔ Apr 2025

Trial initiation date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2L1 • KMT2A • MCL1

Desensitization to calaspargase pegol appears to be less successful than pegaspargase. (PubMed, Blood Adv) - No abstract available

Journal

Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov) - P2 | N=100 | Recruiting | Sponsor: St. Jude Children's Research Hospital | N=145 ➔ 100

Enrollment change • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • T-cell Acute Lymphoblastic Lymphoma

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma (clinicaltrials.gov) - P3 | N=440 | Recruiting | Sponsor: Children's Oncology Group | Active, not recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CRLF2 • PNPLA3 • SOD2

Adding Dasatinib Or Venetoclax To Improve Responses In Children With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (ALL) Or Lymphoma (T-LLY) Or Mixed Phenotype Acute Leukemia (MPAL) (clinicaltrials.gov) - P2 | N=145 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T Cell Non-Hodgkin Lymphoma • T-cell Acute Lymphoblastic Lymphoma

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma (clinicaltrials.gov) - P3 | N=440 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial completion date: Dec 2027 ➔ Dec 2028 | Trial primary completion date: Dec 2027 ➔ Jun 2028

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CRLF2 • PNPLA3 • SOD2

Therapy for Newly Diagnosed Patients With B-Cell Precursor Acute Lymphoblastic Leukemia and Lymphoma (clinicaltrials.gov) - P2 | N=128 | Recruiting | Sponsor: St. Jude Children's Research Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Calaspargase-Pegol-Mknl Combined with BCL-2 and MCL-1 Inhibition for Acute Myeloid Leukemia. (PubMed, Int J Mol Sci) - "Our previous studies have demonstrated that pegcrisantaspase (PegC), a long-acting Erwinia asparaginase, synergizes with the BCL-2 inhibitor Venetoclax (Ven) in vitro and in vivo; however, the anti-leukemic activity of E. coli-derived asparaginases in combination with BCL-2 inhibition, and potential synergy with inhibitors of MCL-1, a key resistance factor of BCL-2 inhibition, has yet to be determined. Using a combination of human AML cells lines, primary samples, and in vivo xenograft mouse models, we established the anti-leukemic activity of the BCL-2 inhibitor S55746 and the MCL-1 inhibitor S63845, alone and in combination with the long-acting E. coli asparaginase calaspargase pegol-mknl (CalPegA)...The S55746-CalPegA combination inhibited protein synthesis and increased eIF4E/4EBP1 interaction, suggesting an inhibition of translational complex formation. These results support the clinical evaluation of CalPegA in combination with BCL-2 inhibition for AML."

Journal • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • BCL2 • EIF4E • EIF4EBP1

Anaphylaxis Associated with Calaspargase in Pediatric Patients with Acute Lymphoblastic Leukemia (ASH 2024) - "There have been different types of asparaginase products used in clinical trials over the years including Native or L-asparaginase, Erwinia asparaginase, Pegaspargase (PEG) and Calaspargase pegol-mknl (Cal-PEG)...Patients receiving Cal-PEG were more likely to have a diagnosis of anaphylaxis (2.9 vs 0.7%; OR 4.59, p<0.001), receive Epinephrine (35.5 vs 17.7%; OR 2.55, p <0.001) and had more admissions to the ICU (2.9 vs 1.7%; OR 1.75, p=0.101)...Venous thrombosis and hemorrhage were less associated with Cal-PEG, even though other toxicities remained the same between the two types of asparaginase. Anaphylaxis rates need to be prospectively confirmed in Children's Oncology Group studies, so that preventive strategy guidelines can be developed for these patients."

Clinical • Acute Lymphocytic Leukemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Leukemia • Oncology • Pancreatitis • Pediatrics • Pulmonary Embolism • Respiratory Diseases

Economic Burden Associated with Switching to Second Line Asparaginase (Recombinant Erwinia) in Pediatrics, Adolescents and Young Adults (AYA) with Acute Lymphoblastic Leukemia (ALL) (ASH 2024) - "Background : Long-acting asparaginases derived from E. coli (pegaspargase [PEG] and calaspargase pegol [CAL-PEG]) are critical components of frontline (1L) chemotherapy regimens in pediatrics, adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL). Mean outpatient costs were $511,810 and $384,396 (p<0.0001) in the non-TDM and TDM groups, respectively.Conclusions : Switch from 1L asparaginase to 2L recombinant Erwinia is relatively common in pediatric and AYA ALL patients which significantly increases treatment costs and HRU, mainly driven by higher outpatient medical costs of recombinant Erwinia. Consideration should be given to performing TDM which may have important implications for mitigating unnecessary switches as well as reducing healthcare burden and achieving substantial cost savings for payers."

Clinical • HEOR • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Managing Hypersensitivity Reactions after Asparaginase Treatment: A Systematic Literature Review (ASH 2024) - "As patients >1 month to <21.5 years old transitioned from pegaspargase (PEG) to calaspargase pegol (CAL-PEG) beginning December 2022, a limited search of recent congress ABSTRACT s was conducted after the original SLR was completed to capture recent data on CAL-PEG. Likewise, reported usage of desensitization protocols is limited and standardization is lacking, demonstrating variable rates of success. A meta-analysis is being explored to further evaluate HSR rates and premedication effectiveness."

Review • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Lymphoma • Oncology

Pharmacokinetics and Pharmacodynamics of Novel Long-Acting Pegylated Recombinant Asparaginase Comparing with Pegaspargase: A Dose-Escalation, Phase Ia Trial in Chinese Healthy Subjects (ASH 2024) - P1 | "PD5K3, a new generation of long-acting asparaginase, is obtained by site-directed mutagenesis of asparaginase sequence derived from Escherichia coli and subsequent saturation modification with polyethylene glycol (5K-SPA-PEG) to achieve a longer half-life and lower immunogenicity.Preclinical studies have shown that the enzyme activity of PD5K3 is comparable to that of pegaspargase and Asparlas. Previously published reports have concluded that ≥ 0.1 IU/ml is an appropriate target level of asparaginase activity associated with complete asparagine depletion, and considered to be effective in the treatment of ALL/LL.Based on the results of phase Ia, a multicenter, dose-escalation and dose-expansion Phase Ib clinical trial is now planned to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PD5K3 in combined chemotherapy regimen in patients. Eligible patients (aged 12 to 40 years) had newly diagnosed ALL/LL or..."

Clinical • P1 data • PK/PD data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

Risk Factors for Calaspargase Pegolmknl Hypersensitivity Reactions in Pediatric Acute Lymphoblastic Leukemia (ASHP 2024) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Comparing Tolerability and Toxicity of Calaspargase pegol and Pegaspargase in Pediatric Leukemia Patients (ASHP 2024) - No abstract available

Clinical • Hematological Malignancies • Leukemia • Oncology • Pediatrics

AALL1821: A Study to Compare Blinatumomab Alone to Blinatumomab With Nivolumab in Patients Diagnosed With First Relapse B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov) - P2 | N=300 | Suspended | Sponsor: National Cancer Institute (NCI) | N=550 ➔ 300

Checkpoint inhibition • Combination therapy • Enrollment change • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • CD19

Calaspargase pegol and pegaspargase cause similar hepatosteatosis in mice. (PubMed, Haematologica) - "Not available."

Journal • Preclinical

Trial Treating Relapsed Acute Lymphoblastic Leukemia With Venetoclax and Navitoclax (clinicaltrials.gov) - P1/2 | N=35 | Active, not recruiting | Sponsor: St. Jude Children's Research Hospital | N=98 ➔ 35 | Trial completion date: Jul 2029 ➔ Mar 2025 | Trial primary completion date: Aug 2025 ➔ Jun 2024

Enrollment change • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma (clinicaltrials.gov) - P3 | N=440 | Active, not recruiting | Sponsor: Children's Oncology Group | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Hepatology • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • CRLF2 • PNPLA3 • SOD2