P2, N=90, Recruiting, Sun Yat-sen University

P3, N=560, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Nov 2028 --> Nov 2034

P2, N=240, Active, not recruiting, Dana-Farber Cancer Institute | Trial completion date: Jul 2025 --> Jul 2027

Rylaze-BI4916 treatment in AML cell lines led to the inhibition of cap-dependent mRNA translation and protein synthesis, as well as a marked decrease in intracellular glutathione levels, a critical cellular antioxidant. Collectively, our results highlight the clinical potential of targeting serine biosynthesis in combination with crisantaspase as a novel therapeutic strategy for AML.

P1/2, N=43, Recruiting, Beijing Tongren Hospital

Pegaspargase (1 IU/g) induces widespread edema and inflammatory infiltration in the pancreas of rats/mice. It greatly activated ATF3 in the acinar, which competed with ATF4 for the Fgf21 promoter, thereby inhibiting the expression of FGF21. Pharmacological replacement of FGF21 (1 mg/kg) or PERK inhibitors (GSK2656157, 25 mg/kg) can significantly mitigate the pancreatic tissue damage and reduce markers of inflammation associated with AAP, representing potential strategies for the prevention and treatment of AAP.

P2, N=210, Recruiting, Fudan University

P1, N=6, Active, not recruiting, University of Maryland, Baltimore | Recruiting --> Active, not recruiting | N=24 --> 6

In conclusion, the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed, advanced stage NKTCL. Dysregulated lipid profile and immunosuppressive signature contributed to treatment resistance, providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

P2/3, N=122, Recruiting, Institut de Recherches Internationales Servier | Trial completion date: Aug 2026 --> Feb 2027

P1, N=20, Recruiting, H. Lee Moffitt Cancer Center and Research Institute | Phase classification: P1b --> P1 | Trial primary completion date: Sep 2027 --> Nov 2024

P3, N=440, Recruiting, Children's Oncology Group | Trial completion date: Dec 2026 --> Dec 2027 | Trial primary completion date: Dec 2026 --> Dec 2027

P1, N=19, Active, not recruiting, Georgetown University | Trial completion date: Dec 2023 --> Jul 2024

Four asparaginase molecules were included in this study, 2 Erwinia-derived - recombinant Erwinia(Rylaze) and native Erwinia (Erwinaze), and 2 E. coli-derived - pegaspargase (Oncaspar) and calaspargase pegol-mknl (Asparlas). Limitations of this study included the nature of the database used, containing mostly outpatient data, and the relatively short study time frame. Future studies with additional data are needed to fully understand the real-world asparaginase use patterns in these patient populations.

One of the main limitations of the frontline pegaspargase (PEG) chemotherapy is the development of hypersensitivity reactions and subsequent development of anti-asparaginase neutralizing antibodies that lead to PEG inactivation...Instead of a single SNP association approach, identifying combinations of variations in pathway specific genes provides a more robust means to predict drug response. Our preliminary results provide a rationale for identification of genome level variations in this cohort and association analysis to establish clinically relevant pharmacogenomics score to optimize PEG treatment.

Recently, Xue et al showed that chidamide in combination with cisplatin, etoposide or gemcitabine showed synergistic effect and reversed the chemotherapy resistance in the relapsed/refractory B-cell lymphoma. This study demonstrates that sandwich CP-GEMOX chemoradiotherapy is a safe and promising approach to managing patients with early-stage ENKTL-NT.

One of the patients with refractory disease underwent further therapy with blinatumomab, inotuzumab, CAR-T and allogeneic stem cell transplantation and is alive at 16 months from diagnosis...Noteworthy adverse effects include neutropenic fever (65%), liver function tests (LFT) abnormalities (70%), and neuropathy from vincristine (70%). Peg-asparaginase administration was associated with pancreatitis in 12%, thromboembolism in 30% and hypersensitivity reactions in 24% requiring switching to alternative forms of asparaginase products (erwinia and Rylaze)... The pediatric-inspired regimen CALGB 10403 was safe and efficacious in our AYA Ph- ALL population with no deaths due to treatment and a 5-year overall survival of 94%. Toxicities, especially from peg-asparaginase, should be closely monitored. While most patients will attain durable remission/cure, the minority with refractory or relapsed disease can still be successfully salvaged to achieve long term survival.

Despite the introduction of asparaginase/pegaspargase-based chemotherapy, the prognosis of patients with advanced NKTCL needs to be improved, and few salvage treatment options are available for relapsed/refractory patients who fail chemotherapy...Immunotherapy has emerged and shown favorable antitumor activity in NKTCL, including monoclonal antibodies targeting immune checkpoint inhibitors, other receptors on the cellular membrane, and cellular immunotherapy, which could enhance immune cells attack on tumor cells. In this review, we provide an overview of recent immunotherapy in NKTCL, focusing on programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1), cytotoxic T lymphocyte-associated protein 4 (CTLA-4), chimeric antigen receptor (CAR) T cells, EBV-specific cytotoxic T lymphocytes, immunomodulatory agents, and other targeted agents, as well as the current progress and challenges in the field.

The clinicopathologic characteristics and prognosis of nasal and nonnasal ENKTL patients are different. Nasal forms patients had superior OS than nonnasal patients, especially in the era of asparaginase.

P1, N=40, Recruiting, New York Medical College | Trial completion date: Dec 2024 --> Dec 2026 | Trial primary completion date: Dec 2023 --> Dec 2025

Pemigatinib, a pan-FGFR inhibitor, is approved to treat intrahepatic cholangiocarcinoma (ICC) harboring FGFR2 fusion mutations...Asn restriction with ASNase or ASNS inhibitors reduced the intracellular Asn, thereby reactivating p53 and sensitizing ICC to F-A Cho-HDO. Our findings highlight the application of genetic engineering therapies in ICC harboring FGFR2 fusions and reveal an axis of adaptation to FGFR2 inhibition that presents a rationale for the clinical evaluation of a strategy combining FGFR2 inhibitors with Asn depletion.

The incidence of serious clinical toxicities was low in this study, particularly pegaspargase-related venous thromboembolism. This suggests that the practice of capping pegaspargase doses at 3750 units, coupled with vigilant monitoring and prophylaxis for pegaspargase-related adverse events, can allow for the inclusion of this drug in the treatment of older individuals.

Based on the response rate and median disease-free period, treatment with pegylated-l-asparaginase is inferior when compared with historical chemotherapy protocols. However, some cats demonstrated an exceptional long disease-free period. Therefore, pegylated-l-asparaginase could be offered as an alternative to corticosteroid therapy alone. Further studies are needed to evaluate the additional benefit over palliative corticosteroid monotherapy.

P3, N=440, Recruiting, Children's Oncology Group | Not yet recruiting --> Recruiting

P3, N=440, Not yet recruiting, Children's Oncology Group | Initiation date: May 2023 --> Oct 2023

This pegarspargase-containing risk-oriented program was feasible and improved outcome of Ph- ALL/LL patients up to 65 years in a multicenter national setting. ClinicalTrials.gov #NCT02067143.

No abstract available

Bio-similar Pegaspargase in combination with chemotherapy was safe and tolerable in the pediatric ALL patients treated according to ICiCLe ALL-14 protocol. Suspected AEs ranged from mild to moderate and hepatic failure and hyperglycemia being severe.

P1, N=19, Active, not recruiting, Georgetown University | Trial completion date: Dec 2024 --> Dec 2023 | Trial primary completion date: May 2023 --> Dec 2022

They were treated with a DDGP regimen (cisplatin/dexamethasone/gemcitabine/pegaspargase), with the female patient evolving to death and the male patient showing a good response to chemotherapy. The prognosis of nasal NK/T-cell lymphoma is variable, with some patients responding well to therapy and others dying from disseminated disease despite aggressive therapy. As NK/T-cell lymphomas are uncommon even in regions where they are most prevalent, multicenter clinical trials are needed to adequately guide future treatments

However, there are only a few reports on the treatment of these patients, which varies widely from watchful waiting to treatment with lactulose, protein restriction, sodium benzoate, and phenylbutyrate to dialysis...Here, we present a cohort of five pediatric patients with symptomatic AIH, which occurred after switching patients from polyethylene glycolated (PEG)- asparaginase to recombinant Crisantaspase Pseudomonas fluorescens (4 patients) or Erwinia (1 patient) asparaginase, and discuss their subsequent management, metabolic workup, and genetic testing...Our data highlights the need for increased awareness of symptomatic AIH, especially when an asparaginase with higher glutaminase activity is used, and its prompt management. The utility and efficacy of this management approach should be systematically investigated in a larger cohort of patients.

P2, N=50, Recruiting, Sun Yat-sen University | Unknown status --> Recruiting | Trial completion date: Mar 2021 --> Mar 2025 | Trial primary completion date: Mar 2021 --> Mar 2025

No treatment-related deaths occurred. First-line sintilimab, anlotinib, and pegaspargase sandwiched with radiotherapy demonstrated promising efficacy in treatment-naïve early-stage ENKTL patients with a favorable safety profile.

No abstract available

When JZP458 is administered 25 mg/m i.m. every 48 h, 93.8% (95% CI: 92.7%, 94.8%) are expected to achieve the last 48-h NSAA level greater than or equal to 0.1 IU/mL. These data supported the i.m. dose of 25 mg/m every 48 h or 25/25/50 mg/m on a MWF dosing schedule in patients with ALL/LBL.

Adverse events of grade 3 or higher occurred in 42 (33.6%) patients in the ESA arm and 81 (65.9%) in the MESA arm. ESA with sandwiched radiotherapy is an effective, low toxicity, non-intravenous regimen with an outpatient design, and can be considered as a first-line treatment option in newly diagnosed early-stage nasal NKTCL.

A total of 233 patients were included in this study, of which most patients were diagnosed with LBL, 120 (54%) patients were older than 14 years, and the male-to-female ratio was around 3:1. Overall, 170 patients received modified BFM-90 regimen, while the rest received modified BFM-95 regimen, both containing pegaspargase. Eventually, 195 (87.4%) patients achieved CR, the estimated 5-year PFS was 70.4% (95%CI: 64.2, 77.2), 5-year overall survival reached 75.5% (95% CI: 69.5, 82.1).

The CTP regimen in combination with radiotherapy as first-line treatment preliminarily indicated effectiveness for ENKTL at high-risk stages I and II. The patients had high CRR and controllable adverse reactions. (NCT04414969)

In summary, the results support the conclusion that the PK exposure of pegaspargase after IV administration at the dose of 2,500 U/m 2 does not depend on the drug formulation. Pharmacokinetics and safety results of this study are consistent with previously observed pegaspargase data. Pediatric, Pharmacokinetic, Acute lymphoblastic leukemia

The combination of camrelizumab, low-dose apatinib and pegaspargase followed by radiotherapy was effective in treating patients with newly diagnosed stage I/II NK/TCL, with acceptable safety profiles. Long-term follow-up isongoing to determine the survival benefits of the regimen. Clinical trial, Immune therapy, Anti-angiogenesis, NK-T cells