long-acting Erwinia asparaginase (JZP341) / Jazz, Ligand - LARVOL DELTA

Overcoming Venetoclax (Ven) Resistance through Glutamine (Gln) Depletion: Final Analysis of the Phase 1 Trial of Ven and Pegcrisantaspase (PegC) Combination in Relapsed and Refractory (R/R) Acute Myeloid Leukemia (AML) (ASH 2023) - P1 | "We reported in vitro and in vivo depletion of Gln induced by long-acting Erwinia asparaginase, PegC, inhibited proliferation of complex karyotype (CK) AML and synergistically enhanced the antiapoptotic activity of Ven-mediated antagonism of Bcl-2 by decreasing the expression of proteins such as Mcl-1, whose translation is cap-dependent...Pt 31 (post-alloHSCT relapsed AML with FLT3-ITD) who had persistent disease after gilteritinib achieved an MRD-negative CRi, pending 2nd alloHSCT... VenPegC is a novel regimen that can induce complete remission in some heavily pretreated R/R AML patients, even with previous exposure to Ven. Pts with RUNX1 mutation, whose translation depends on pheIF4E, may benefit further from this regimen."

IO biomarker • P1 data • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Dyslipidemia • Hematological Disorders • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Leukemia • Oncology • Pancreatitis • Transplantation • BCL2 • CSF3R • EIF4E • EIF4EBP1 • FLT3 • MCL1 • NRAS • PTPN11 • RUNX1 • TP53

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

A JZP341 Study in Adult Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Terminated | Sponsor: Jazz Pharmaceuticals | Trial completion date: Nov 2024 ➔ Apr 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Nov 2024 ➔ Apr 2024; The study was terminated based on a business decision by the Sponsor.

Metastases • Trial completion date • Trial primary completion date • Trial termination • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR

A JZP341 Study in Adult Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: Jazz Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=88 ➔ 12 | Trial completion date: Nov 2027 ➔ Nov 2024 | Trial primary completion date: Nov 2027 ➔ Nov 2024

Enrollment change • Enrollment closed • Metastases • Trial completion date • Trial primary completion date • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR

Comprehensive Plasma Amino Acid Analysis Following Administration of Short- and Long-Acting Erwinia Asparaginase (Crisantaspase) Demonstrated Significant Increase in Plasma Serine and Glycine Levels (ASH 2022) - P1 | "Mouse plasma samples were from studies that included treatment with pegcrisantaspase (PegC), a long-acting Erwinia-derived asparaginase, in both immunodeficient and immunocompetent mice. We report a comprehensive evaluation of plasma AA alterations in both mice and humans treated with crisantaspase. We observed a reproducible crisantaspase-induced increase in plasma Ser and Gly, which we are currently exploiting for synergism with other AML treatment modalities."

Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology

A JZP341 Study in Adult Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=88 | Recruiting | Sponsor: Jazz Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR

JZP341 Phase 1 Dose-Finding Study in Adult Participants With Advanced or Metastatic Solid Tumors (clinicaltrials.gov) - P1 | N=88 | Not yet recruiting | Sponsor: Jazz Pharmaceuticals

New P1 trial • Colorectal Adenocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • EGFR