Rylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn)

P2, N=30, Not yet recruiting, University of Washington

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2027 --> Dec 2028 | Initiation date: Oct 2024 --> Jan 2025 | Trial primary completion date: Dec 2027 --> Dec 2028

P=N/A, N=10, Recruiting, Mayo Clinic

P3, N=280, Active, not recruiting, Children's Oncology Group | Trial completion date: Jun 2024 --> Jul 2025

P2, N=80, Recruiting, Children's Oncology Group | Trial completion date: Dec 2024 --> Mar 2026 | Trial primary completion date: Dec 2024 --> Mar 2026

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.

P2, N=171, Not yet recruiting, National Cancer Institute (NCI) | Initiation date: Apr 2024 --> Jul 2024

P2, N=171, Not yet recruiting, National Cancer Institute (NCI)

P3, N=1400, Active, not recruiting, Children's Oncology Group | Recruiting --> Active, not recruiting

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 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.

P3, N=6720, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2030 --> Jun 2029 | Trial primary completion date: Mar 2030 --> Jun 2029

P3, N=6720, Recruiting, National Cancer Institute (NCI) | Suspended --> Recruiting

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.

P2/3, N=793, Active, not recruiting, St. Jude Children's Research Hospital | Recruiting --> Active, not recruiting

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.

We determined that short-acting crisantaspase (Rylaze) inhibited the proliferation of several AML cell lines with pharmacologically relevant IC50 values ranging from 0.001 to 0.08 µg/mL... Simultaneous targeting of Ser and Gln metabolism for AML treatment shows promising results in vitro with great potential for translation into clinical practice with clinically available asparaginases, and other glutamine modulators. Ongoing work is focused on the design of a more potent pharmacologic inhibitor of PHGDH to combine with crisantaspase as a novel treatment approach for AML.

Here, we report synergistic anti-leukemic activity of the BCL-2 inhibitor venetoclax (Ven) and the asparaginase formulation Pegylated Crisantaspase (PegC) in CK-AML in vitro and in vivo...Superiority of Ven-PegC, compared to single drugs, and, importantly, the clinically utilized Ven-azacitidine combination, was also demonstrated in vivo in CK-AML...In vivo, Ven-PegC treatment completely depleted plasma glutamine and asparagine and inhibited mRNA translation and cellular protein synthesis. Since this novel mechanistically-rationalized regimen combines two drugs already in use in acute leukemia treatment, we plan a clinical trial of the Ven-PegC combination in relapsed/refractory CK-AML.