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

Preliminary results of an open-label, single-arm phase 2/3 trial (SPARK-ALL) of calaspargase pegol in adults with newly diagnosed Philadelphia chromosome–negative acute lymphoblastic leukemia. (ASCO 2026) - P2/3 | "In patients (pts) <21 years, calaspargase pegol (Cal-PEG) provides more sustained asparagine depletion than pegaspargase. Cal-PEG has a safety profile consistent with asparaginase class toxicity and, as part of multidrug chemotherapy regimen, provides sustained asparagine depletion in newly diagnosed Ph− ALL pts aged ≥22 years. In light of the observed high-grade TRAEs, future studies will evaluate different Cal-PEG doses for this pt population."

Clinical • P2/3 data • Acute Lymphocytic Leukemia • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hypertriglyceridemia • Immunology • Ischemic stroke • Leukemia • Pulmonary Embolism • Respiratory Diseases

Phase 1 of Calaspargase Pegol-mknl W/ Cytarabine and Idarubicin in Newly Diagnosed AML (clinicaltrials.gov) - P1 | N=6 | Active, not recruiting | Sponsor: West Virginia University | Trial completion date: Dec 2025 ➔ Feb 2030 | Trial primary completion date: Dec 2025 ➔ Feb 2030

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology

AALL1631: Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (clinicaltrials.gov) - P3 | N=352 | Active, not recruiting | Sponsor: Children's Oncology Group | Trial primary completion date: Sep 2027 ➔ Jun 2026

Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • ABL1 • CSF1R • PDGFRA • PDGFRB

Large Single Center Respective Study - Asparaginase Induced Hyperammonemia (SSIEM 2026) - "This was a retrospective study of patients who received at least one dose of an asparaginase product (Erwinaze®, Rylaze®, Oncaspar®, or Asparlas®) and a documented ammonia level from January 1, 2015 to December 31, 2025 at Ann & Robert H. Lurie Children's Hospital of Chicago. Our study showed that a relatively small percentage of patients receiving asparaginase products experienced hyperammonemia and hyperammonemic crises. Establishing awareness for identifying patients with symptoms of hyperammonemia, implementing a standardized protocol for monitoring ammonia levels post asparaginase injections and infusions and tailoring metabolic management are important aspects for mitigating serious acute and chronic outcomes associated with asparaginase products."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia

CASPER: Calaspargase Pegol-Mnkl and Cobimetinib for the Treatment of Locally Advanced or Metastatic Pancreatic Cancer (clinicaltrials.gov) - P1 | N=15 | Completed | Sponsor: OHSU Knight Cancer Institute | Active, not recruiting ➔ Completed | Trial completion date: Oct 2026 ➔ Jun 2026

Trial completion • Trial completion date • Oncology • Pancreatic Cancer • Solid Tumor

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 primary completion date: Jun 2028 ➔ Sep 2026

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

PKPD-Based Translational Modeling of Calaspargase Pegol Preclinical Activity in Hepatocellular Carcinoma. (PubMed, Eur J Drug Metab Pharmacokinet) - "The results indicate that PKPD TGI modeling can be used to build a preclinical to clinical translational framework to predict the exposure-response relationship in patients with HCC and to inform dosing strategies or trial designs for solid tumors."

Journal • Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Oncology • Pediatrics • Solid Tumor

Testing Blinatumomab With or Without Revumenib in Patients With B-cell Acute Lymphoblastic Leukemia With a Genetic Change Requiring More Treatment (clinicaltrials.gov) - P2 | N=90 | Not yet recruiting | Sponsor: SWOG Cancer Research Network

New P2 trial • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • CD19 • KMT2A

Economic burden associated with switching from frontline pegaspargase or calaspargase pegol to second-line recombinant Erwinia in pediatrics and adolescents/young adults with acute lymphoblastic leukemia. (PubMed, J Med Econ) - "Switching from 1 L PEG/CAL-PEG to 2 L recombinant Erwinia is associated with higher healthcare costs. Consideration should be given to TDM, which may mitigate unnecessary switches of asparaginase."

HEOR • Journal • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics

Induction Chemoimmunotherapy and AlloSCT in Advanced Stage Mature T/NK-Cell Lymphoma in CAYA (ASPHO 2026) - P1 | "Cohort 1 receives 2 Induction cycles [daratumumab/dexamethasone/methotrexate/ifosfamide/calaspargase pegol-mknl/etoposide (D-SMILE)]. The addition of immunotherapy with daratumumab or brentuximab vedotin to induction chemotherapy and consolidation with RTC and alloSCT in CAYA patients with M-TCL has been safe, feasible and potentially will result in improved outcomes. Overcoming clinical complications related to disease processes, such as HLH, remain challenging"

Metastases • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Natural Killer/T-cell Lymphoma • Respiratory Diseases

A Study Testing the Combination of Dasatinib or Imatinib to Chemotherapy Treatment With 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) - P2 | N=222 | Recruiting | Sponsor: National Cancer Institute (NCI) | Phase classification: P3 ➔ P2

Phase classification • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CD19 • CSF1R • PDGFRB

Variability in Calaspargase Pegol Administration and Monitoring Across U.S. Pediatric Oncology Centers. (PubMed, Pediatr Blood Cancer) - "This survey reveals substantial variability in sc-PEG administration and monitoring practices across U.S. pediatric cancer centers, underscoring the lack of standardized, evidence-based guidelines. These findings highlight the need for prospective research to define optimal strategies and improve the accuracy of hypersensitivity recognition with sc-PEG."

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

Hepatotoxicity from L-asparaginase is associated with lipid changes in a mouse model (AACR 2024) - "L-asparaginase (Calaspargase-pegol, PEG) is currently an important component of acute lymphoblastic leukemia (ALL) treatment in children, adolescents, and young adults...As low PC has been shown to induce fatty liver, this finding implies that PEG might induce steatosis via reduction in PC and its precursor, PE. Future work will investigate the mechanisms by which PEG reduces liver PE and PC levels, and whether this is causally related to steatosis and hepatotoxicity."

Preclinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Oncology

Asparaginases-Treatment potential for the biomarker selected hepatocellular carcinoma (HCC) population (AACR 2024) - "This activity was lost in models with lesser degrees of methylation indicating a strict threshold of promoter methylation for efficacy. These data confirm and extend previous findings that hypermethylation of the ASNS promoter has a synthetic lethal relationship with Asn-depleting therapies including Asparlas and highlight the need to carefully define the minimum threshold of hypermethylation to select HCC patients who could potentially benefit from Asparlas treatment."

Biomarker • Clinical • Acute Lymphocytic Leukemia • Gastric Cancer • Gastrointestinal Cancer • Hematological Malignancies • Hepatocellular Cancer • Leukemia • Oncology • Solid Tumor • T Acute Lymphoblastic Leukemia

Evaluation of Prolonged Asparaginase Activity Levels After Calaspargase Pegol Administration (clinicaltrials.gov) - P=N/A | N=20 | Not yet recruiting | Sponsor: Mayo Clinic | Trial completion date: Dec 2027 ➔ Dec 2028 | Initiation date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Dec 2027 ➔ Dec 2028

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

Incidence of Hypersensitivity Reactions between Pegaspargase and Calaspargase Pegol in Pediatric Acute Lymphoblastic Leukemia (ALL) (HOPA 2026) - "Calaspargase pegol had a statistically significantly higher incidence of hypersensitivity reactions compared to the pegaspargase group when analyzed at Riley Children's Hospital. This supports the review of institutional protocols to maximize HSR management, provider education, and potential formulary modifications. We expect that expanding this study to include data from Nationwide Children's Hospital will further strengthen these results."

Clinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Immunology • Leukemia • Pancreatitis • Pediatrics

DFCI 21-757: Venetoclax Basket Trial for High Risk Hematologic Malignancies (clinicaltrials.gov) - P1 | N=30 | Recruiting | Sponsor: Andrew E. Place, MD | Active, not recruiting ➔ Recruiting | N=13 ➔ 30 | Trial completion date: Jul 2028 ➔ Jul 2030 | Trial primary completion date: Jul 2026 ➔ Jul 2028

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

CalPeg for Newly Diagnosed Acute Lymphoblastic Leukemia (ALL) (clinicaltrials.gov) - P1 | N=7 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting ➔ Recruiting | Trial primary completion date: Jun 2025 ➔ Oct 2026

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

AALL1732: Inotuzumab Ozogamicin and Post-Induction Chemotherapy in Treating Patients With High-Risk B-ALL, Mixed Phenotype Acute Leukemia, and B-LLy (clinicaltrials.gov) - P3 | N=5951 | Recruiting | Sponsor: Children's Oncology Group | Trial completion date: Mar 2030 ➔ Mar 2032 | Trial primary completion date: Mar 2030 ➔ Mar 2032

Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Central Nervous System Leukemia • CNS Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Oncology

SPARK-ALL: Calaspargase Pegol in Adults With ALL (clinicaltrials.gov) - P2/3 | N=42 | Terminated | Sponsor: Institut de Recherches Internationales Servier | N=122 ➔ 42 | Trial completion date: Feb 2026 ➔ Mar 2025 | Active, not recruiting ➔ Terminated; Sponsor decision

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

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: Mar 2026 ➔ Jun 2026

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

Shield or Security Blanket? Premedication Use With Calaspargase-Pegol. (PubMed, Pediatr Blood Cancer) - No abstract available

Journal • Hematological Malignancies • Immunology • Leukemia • Oncology

Comparing Safety Profiles of Calaspargase pegol-mknl and Pegaspargase: A Retrospective Analysis of Adverse Events in Acute Lymphoblastic Leukemia Treatment (ASHP 2025) - No abstract available

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia

Tolerability of Calaspargase Pegol Compared to Pegaspargase in Patients with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma at a Pediatric Institution (ASHP 2025) - No abstract available

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoblastic Lymphoma • Lymphoma • Pediatrics

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 • Septic Shock • BCL2