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

A phase I study of venetoclax in combination with multiagent cytotoxic chemotherapy for children and adolescents with relapsed or refractory acute lymphoblastic leukemia or mixed phenotype acute leukemia: Results of the dose determination cohort (ASH 2025) - P1 | "Cohort C is testing VEN in combination with multiagentchemotherapy (dexamethasone, vincristine, doxorubicin, and calaspargase pegol (Cal-peg)) based onDFCI 16-001 high-risk Induction IA (Vrooman et al Blood 2024) in patients (pts) 1-21 years of age withrelapsed/refractory ALL or MPAL. There was excess gastrointestinal toxicity at DL1, likely related to prolonged exposure to VENin combination with dexamethasone, which has not been seen at DL-1. Importantly, overall observedtoxicity is comparable to reported toxicity rates for multiagent reinduction regimens (Hogan et alHaematologica 2025), suggesting that VEN does not further increase toxicity of this regimen."

Clinical • Combination therapy • IO biomarker • P1 data • Acute Lymphocytic Leukemia • Anorexia • Diabetes • Febrile Neutropenia • Gastrointestinal Disorder • Hypertension • Infectious Disease • Mucositis • Neutropenia • Pancreatitis • Pediatrics • Septic Shock • BCL2

Evaluation of Prolonged Asparaginase Activity Levels After Calaspargase Pegol Administration (clinicaltrials.gov) - P=N/A | N=20 | Not yet recruiting | Sponsor: Mayo Clinic

New trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology

RISK FACTORS ASSOCIATED WITH HYPOGLYCEMIA DURING ASPARAGINASE THERAPY AND STRATEGIES FOR MANAGEMENT IN PEDIATRIC PATIENTS WITH LEUKEMIA (SIOP 2025) - " Ninety-four patients received calaspargase pegol (CAL-PEG) or recombinant Erwinia asparaginase, with 19 individuals experiencing at least one episode of AAH...Of these 12 patients, 83.3% had not yet received mercaptopurine, a known risk factor for hypoglycemia... Incidence of AAH was 20% among our cohort with most episodes presenting early in therapy after one dose of CAL-PEG. Identifying patients at an increased risk for AAH allows for enhanced glucose monitoring, aiming to reduce severe hypoglycemic events and hospitalizations in this population."

Clinical • Acute Lymphocytic Leukemia • Diabetes • Genetic Disorders • Hematological Malignancies • Hypoglycemia • Leukemia • Obesity • Pediatrics

CALASPARGASE PEGOL ALGORITHM TO EVALUATE ASPARAGINASE ACTIVITY (SIOP 2025) - "Conclusions These results provide an algorithm to guide the decision to switch to Erwinia asparaginase. Additionally, we are developing an on-line therapeutic monitoring tool to guide dose adjustments for CAL-PEG to maintain activity >0.1 IU/mL for at least 21 days."

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

COLLABORATION WITH CALASPARGASE: A REAL-WORLD MULTICENTER TOXICITY ANALYSIS FOR AT RISK PEDIATRIC AND ADOLESCENT YOUNG ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA/LYMPHOMA (SIOP 2025) - "Conclusions Our multicenter real-world analysis of Cal-PEG demonstrates high rates of AAT. An expansion of the cohort, assessment of risk factors for AAT, and comparisons to historical controls treated with pegaspargase are ongoing."

Adverse events • Clinical • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Dyslipidemia • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Immunology • Leukemia • Lymphoma • Obesity • Pancreatitis • Pediatrics • Thrombosis

CASPER: Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Active, not recruiting | Sponsor: OHSU Knight Cancer Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • Oncology • Pancreatic Cancer • Solid Tumor

SPARK-ALL: Calaspargase Pegol in Adults With ALL (clinicaltrials.gov) - P2/3 | N=122 | Active, not recruiting | Sponsor: Institut de Recherches Internationales Servier | Trial primary completion date: Feb 2026 ➔ Mar 2025

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

Asparagine Synthetase promoter hypermethylation is required, but not sufficient, for sensitivity to Asparlas in patient-derived models of hepatocellular carcinoma. (PubMed, Eur J Pharmacol) - "However, when a panel of patient derived xenograft models representing a range of pASNSmet levels was tested we found that high pASNSmet levels were required but not necessarily sufficient to confer sensitivity to treatment with Asparlas. Collectively, these results are in support of ASNS promoter hypermethylation as a targetable phenotype but indicate that pASNSmet alone is not a viable biomarker of this phenotype, and that significant advancements in our understanding of the underlying biology may be required before asparaginase-depleting therapy can be successfully implemented clinically in HCC."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia • ASNS

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 | Recruiting | Sponsor: M.D. Anderson Cancer Center | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

Venetoclax Basket Trial for High Risk Hematologic Malignancies (clinicaltrials.gov) - P1 | N=13 | Active, not recruiting | Sponsor: Andrew E. Place, MD | Recruiting ➔ Active, not recruiting | N=92 ➔ 13

Enrollment change • Enrollment closed • Pan tumor • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • ABL1 • BCL2 • BCR • FLT3 • IKZF1 • KMT2A

AALL2331: Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL) (clinicaltrials.gov) - P2/3 | N=1708 | Not yet recruiting | Sponsor: Children's Oncology Group | Initiation date: Sep 2025 ➔ Mar 2026

Trial initiation date • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

Prolonged Therapeutic Serum Asparaginase Activity Levels After Administration of Calaspargase Pegol. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal

Exploring the Effect of Calaspargase Pegol on the Coagulation System in Pediatric Acute Lymphoblastic Leukemia (ALL) Patients: Pilot Study (clinicaltrials.gov) - P=N/A | N=15 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

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

Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL) (clinicaltrials.gov) - P2/3 | N=1708 | Not yet recruiting | Sponsor: Children's Oncology Group

New P2/3 trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia

CalPeg for Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: New York Medical College | Trial completion date: Dec 2026 ➔ Dec 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Hematological Malignancies • Hepatosplenic T-cell Lymphoma • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Transplantation

Comparing Tolerability and Toxicity of Calaspargase-Pegol and Pegaspargase in Pediatric Leukemia Patients. (PubMed, J Pediatr Hematol Oncol) - "However, calaspargase-pegol did require more conversions to short-acting asparaginase therapy. Additional monitoring and preventative measures should be utilized to prevent calaspargase-pegol-associated adverse effects."

Journal • Dyslipidemia • Hematological Malignancies • Hypertriglyceridemia • Immunology • Leukemia • Oncology • Pediatrics

Severe hypertriglyceridemia associated with calaspargase pegol. (PubMed, Leuk Lymphoma) - "Herein we describe our clinical observations of six patients who experienced significant hypertriglyceridemia following exposure to calaspargase pegol, warranting intensive care in several cases. Potential confounding risk factors and management strategies of this presumed toxicity are explored."

Journal • Critical care • Dyslipidemia • Hypertriglyceridemia • Severe Hypertriglyceridemia

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=461 | Recruiting | Sponsor: National Cancer Institute (NCI) | Suspended ➔ Recruiting | N=300 ➔ 461

Enrollment change • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Oncology • CD19

Exploring the Effect of Calaspargase Pegol on the Coagulation System in Pediatric Acute Lymphoblastic Leukemia (ALL) Patients: Pilot Study (clinicaltrials.gov) - P=N/A | N=15 | Not yet recruiting | Sponsor: Mayo Clinic

New trial • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics

OPTIMIZING ASPARAGINASE HYPERSENSITIVITY MANAGEMENT: REAL-WORLD EVIDENCE ON ASPARAGINASE SWITCHING PRACTICES AND GUIDELINE ADHERENCE (EHA 2025) - "Background: Calaspargase pegol (CAL-PEG) is a critical component of frontline treatment for acute lymphoblastic leukemia (ALL), contributing significantly to excellent outcomes... About 38% of patients who switched to recombinant Erwinia did so despite having ≤ grade 2 HSRs, with most occurring in induction. True antibody-mediated HSRs are rare after initial asparaginase exposure and some of these may represent infusion reactions. TDM can help distinguish true HSRs from infusion reactions, but its underuse suggests an opportunity to improve real-world management and reduce unnecessary asparaginase formulation switches."

Adherence • Clinical • HEOR • Real-world • Real-world evidence • Acute Lymphocytic Leukemia • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics

Application of a Multiomics Imaging Workflow to Explore Asparlas Treatment in Solid Tumors. (PubMed, Anal Chem) - "This study established a multiomics imaging approach and demonstrated its applicability in elucidating the metabolic changes in tumor tissue consequent to Asparlas treatment. Furthermore, it highlights the added value of multiomics imaging in pharmaceutical research and development."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

A Study Comparing the Combination of Dasatinib or Imatinib and Chemotherapy Treatment With or Without Blinatumomab for Children, Adolescents, and Young Adults With Philadelphia Chromosome Positive (Ph+) or ABL-Class Philadelphia Chromosome-Like (Ph-Like) B-Cell Acute Lymphoblastic Leukemia (B-ALL) (clinicaltrials.gov) - P3 | N=222 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting | N=680 ➔ 222

Enrollment change • Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CD19 • CSF1R • KIT • PDGFRA • PDGFRB

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 | Trial completion date: Mar 2025 ➔ Feb 2027

Trial completion date • Acute Lymphocytic Leukemia • Hematological Malignancies • 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=153 | Recruiting | Sponsor: National Cancer Institute (NCI) | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology