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DRUG CLASS:

Arginine depleter

3ms
ADI-PEG 20 Plus Radiotherapy and Temozolomide in Subjects with Glioblastoma Multiforme (clinicaltrials.gov)
P2, N=100, Recruiting, Polaris Group | Phase classification: P1b --> P2 | N=32 --> 100
Phase classification • Enrollment change
|
temozolomide • Hepacid (pegargiminase)
5ms
Trial completion date
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
|
carboplatin • cabazitaxel • Hepacid (pegargiminase)
5ms
Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC) (clinicaltrials.gov)
P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Sep 2027 | Trial primary completion date: Dec 2025 --> Sep 2027
Trial completion date • Trial primary completion date
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
|
carboplatin • cabazitaxel • Hepacid (pegargiminase)
7ms
ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers (clinicaltrials.gov)
P1/2, N=114, Recruiting, Washington University School of Medicine | Trial completion date: Jun 2032 --> Dec 2032 | Trial primary completion date: Jun 2027 --> Dec 2027
Trial completion date • Trial primary completion date • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
gemcitabine • docetaxel • Hepacid (pegargiminase)
9ms
Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma (clinicaltrials.gov)
P1/2, N=35, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
|
ifosfamide • Hepacid (pegargiminase) • mesna
10ms
Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma (clinicaltrials.gov)
P1/2, N=35, Not yet recruiting, Washington University School of Medicine | Trial completion date: Nov 2027 --> Feb 2028 | Initiation date: Jan 2024 --> Apr 2024 | Trial primary completion date: Nov 2025 --> Feb 2026
Trial completion date • Trial initiation date • Trial primary completion date • Combination therapy
|
ifosfamide • Hepacid (pegargiminase) • mesna
10ms
Enrollment open
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • PTEN mutation • LDH elevation
|
carboplatin • cabazitaxel • Hepacid (pegargiminase)
1year
Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma (clinicaltrials.gov)
P1/2, N=35, Not yet recruiting, Washington University School of Medicine | Trial completion date: Aug 2027 --> Nov 2027 | Initiation date: Oct 2023 --> Jan 2024 | Trial primary completion date: Aug 2025 --> Nov 2025
Trial completion date • Trial initiation date • Trial primary completion date
|
ifosfamide • Hepacid (pegargiminase) • mesna
1year
A Study Evaluating Atezolizumab and Bevacizumab Plus ADI-PEG 20 in Patients With Locally Advanced / Metastatic Hepatocellular Carcinoma (clinicaltrials.gov)
P1/2, N=0, Withdrawn, M.D. Anderson Cancer Center | N=10 --> 0 | Trial completion date: May 2025 --> Nov 2023 | Initiation date: Feb 2024 --> Aug 2023 | Not yet recruiting --> Withdrawn | Trial primary completion date: May 2025 --> Nov 2023
Enrollment change • Trial completion date • Trial initiation date • Trial withdrawal • Trial primary completion date • Metastases
|
Avastin (bevacizumab) • Tecentriq (atezolizumab) • Hepacid (pegargiminase)
1year
New P1/2 trial
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
|
TP53 mutation • PTEN mutation • LDH elevation
|
carboplatin • cabazitaxel • Hepacid (pegargiminase)
over1year
A novel combination therapy of arginine deiminase and an arginase inhibitor targeting arginine metabolism in the tumor and immune microenvironment. (PubMed, Am J Cancer Res)
Importantly, mechanistic analysis indicated that the processes of the cell cycle, ribonucleoprotein complex biogenesis, and ribosome biogenesis were upregulated after combination treatment. This study implied the possibility of L-Norvaline as a modulator of the immune response in cancer and provided a new potential therapy combined with ADI-PEG 20.
Journal • Combination therapy
|
CD8 (cluster of differentiation 8) • S100A8 (S100 Calcium Binding Protein A8) • S100A9 (S100 Calcium Binding Protein A9) • ASS1 (Argininosuccinate synthase 1) • CCR7 (Chemokine (C-C motif) receptor 7)
|
Hepacid (pegargiminase)
over1year
A role for macrophages under cytokine control in mediating resistance to ADI-PEG20 (pegargiminase) in ASS1-deficient mesothelioma. (PubMed, Pharmacol Rep)
Collectively, our data indicate that ADI-PEG20-inducible cytokines orchestrate argininosuccinate fuelling of ASS1-deficient mesothelioma by macrophages. This novel stromal-mediated resistance pathway may be leveraged to optimize arginine deprivation therapy for mesothelioma and related arginine-dependent cancers.
Journal
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ASS1 (Argininosuccinate synthase 1) • CXCR2 (Chemokine (C-X-C motif) receptor 2)
|
VEGFA elevation • ASS1 negative • VEGFA expression
|
Hepacid (pegargiminase) • clodronate disodium
over1year
Enrollment open • Combination therapy
|
EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
|
EGFR mutation
|
gemcitabine • docetaxel • Hepacid (pegargiminase)
almost2years
L-arginine depletion causes different proliferation responses in breast cancer subtypes - Relation to gene expression profiles of L-arginine metabolic pathways (AACR 2023)
Gene expression patterns of MCF-12A and MCF-7 were very similar.In conclusion, metabolic fingerprinting reveals complex and differential regulation of L-arginine pathways in breast cancer cell lines. These analyses may help to understand differences in proliferation during L-arginine depletion, thus offering a perspective to further personalize treatment options within classical molecular breast cancer subtypes.
Gene Expression Profile
|
ER (Estrogen receptor) • ASS1 (Argininosuccinate synthase 1) • ARG2 (Arginase 2)
|
ER positive
almost2years
The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C. (PubMed, Cancer Cell Int)
Therapeutic utilization of a metabolic defect in GBM along with cytostatic therapy provides a novel combination approach. Whether this SpyADI/MitA regimen will provide a safe alternative to combat GBM, will have to be addressed in subsequent (pre-)clinical trials.
Journal
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ATF4 (Activating Transcription Factor 4)
almost2years
Arginase 1 is a key driver of immune suppression in pancreatic cancer. (PubMed, Elife)
Treatment of established tumors with the arginase inhibitor CB-1158 exhibited further increased CD8 T cell infiltration, beyond that seen with the macrophage-specific knockout, and sensitized the tumors to anti-PD1 immune checkpoint blockade. Our data demonstrate that Arg1 drives immune suppression in pancreatic cancer by depleting Arginine and inhibiting T cell activation.
Journal • PD(L)-1 Biomarker • IO biomarker
|
CD8 (cluster of differentiation 8) • ARG2 (Arginase 2)
|
ARG1 overexpression
|
numidargistat (INCB001158)
almost2years
Bcl-xL prevents the arginine starvation induced by PEGylated arginine deiminase (ADI-PEG20) from inducing apoptosis (ESMO-TAT 2023)
Methods Cell lines were treated with ADI-PEG20 and A-1331852 (Bcl-xL inhibitor) and monitored for cell death using the Incucyte. Bcl-xL inhibition synergies with ADI-PEG20 to induce apoptosis. This study provides the preclinical rationale for combining ADI-PEG20 with next generation Bcl-xL inhibitors such as the Bcl-xL PROTAC in a phase I clinical trial.
PARP Biomarker • IO biomarker
|
BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • ASS1 (Argininosuccinate synthase 1) • CASP3 (Caspase 3)
|
BCL2 expression • MCL1 expression
|
A-1331852 • Hepacid (pegargiminase)
almost2years
Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma (clinicaltrials.gov)
P1, N=9, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> Jan 2023 | Trial primary completion date: Apr 2024 --> Jan 2023
Trial completion • Trial completion date • Trial primary completion date • Checkpoint inhibition • Metastases
|
GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11) • CYSLTR2 (Cysteinyl Leukotriene Receptor 2) • PLCB4 (Phospholipase C Beta 4)
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Hepacid (pegargiminase)
almost2years
BAP1 loss is associated with higher ASS1 expression in epithelioid mesothelioma: implications for therapeutic stratification. (PubMed, Mol Cancer Res)
Alterations in arginine metabolism may sensitise cells to metabolic drugs and we find that BAP1-negative/ASS1-expressing MPM cell lines are more sensitive to ASS1 inhibition, although not to inhibition of purine synthesis by mizoribine. Importantly, BAP1w-/KO MeT5A become desensitised to arginine-deprivation by pegylated arginine deiminase (ADI-PEG20), phenocopying BAP1-negative/ASS1-expressing MPM cell lines. Implications: Our data reveal an inter-relationship between BAP1 and arginine metabolism, providing a potential means of identifying epithelioid MPM patients likely to benefit from ADI-PEG20.
Journal • BRCA Biomarker
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BRCA1 (Breast cancer 1, early onset) • BAP1 (BRCA1 Associated Protein 1) • ASS1 (Argininosuccinate synthase 1)
|
BAP1 mutation • ASS1 negative • BAP1 negative
|
Bredinin (mizoribine) • Hepacid (pegargiminase)
almost2years
Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma (clinicaltrials.gov)
P1, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2023 --> Apr 2024 | Trial primary completion date: Apr 2023 --> Apr 2024
Trial completion date • Trial primary completion date • Checkpoint inhibition • Metastases
|
GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11) • CYSLTR2 (Cysteinyl Leukotriene Receptor 2) • PLCB4 (Phospholipase C Beta 4)
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Hepacid (pegargiminase)
2years
WWOX-rs13338697 genotype predicts therapeutic efficacy of ADI-PEG 20 for patients with advanced hepatocellular carcinoma. (PubMed, Front Oncol)
The WWOX-rs13338697-GG genotype was associated with lower tissue WWOX and ASS1 levels and higher pretreatment plasma arginine levels, resembling an arginine auxotrophic phenotype requires excessive extracellular arginine supply. Silencing WWOX to mimic HCC with the WWOX-rs13338697-GG genotype further stimulated HCC cell response to hypoxia through increased HIF1A expression, leading to further reduction of ASS1 and thus increased cell susceptibility to ADI-PEG 20.
Journal
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • ASS1 (Argininosuccinate synthase 1)
|
HIF1A expression
|
5-fluorouracil • leucovorin calcium • Hepacid (pegargiminase)
2years
Enhancement of anti-tumor activity in melanoma using arginine deiminase fused with 30Kc19α protein. (PubMed, Appl Microbiol Biotechnol)
The fusion protein demonstrated selective cytotoxicity and reduced drug resistance in melanoma cells, thus would be a promising strategy for the improved efficacy in melanoma treatment. KEY POINTS: • Fusion of ADI with 30Kc19α enhances soluble expression and productivity of recombinant ADI in E. coli • 30Kc19α protects ADI from the proteolytic degradation by shielding effect, helping ADI to remain active • Intracellular delivery of ADI by 30Kc19α overcomes ADI resistance in melanoma cells by degrading intracellularly expressed arginine.
Journal
|
MMP2 (Matrix metallopeptidase 2) • ASS1 (Argininosuccinate synthase 1)
2years
Annexin A2/TLR2/MYD88 pathway induces arginase 1 expression in tumor-associated neutrophils. (PubMed, J Clin Invest)
Mechanistically, ANXA2 signaled through the TLR2/MYD88 axis in neutrophils to induce ARG1 mRNA expression. The current study describes what we believe to be a novel mechanism by which ARG1 mRNA expression is regulated in neutrophils in cancer and highlights the central role that neutrophil lineage cells play in the suppression of tumor-infiltrating lymphocytes.
Journal
|
MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • ARG1 (Arginase 1) • TLR2 (Toll Like Receptor 2)
over2years
Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy. (PubMed, Lung Cancer (Auckl))
Small cell lung cancer (SCLC) displays marked arginine auxotrophy due to inactivation of the rate-limiting enzyme argininosuccinate synthetase 1 (ASS1), and as a consequence may be targeted with pegylated arginine deiminase or ADI-PEG20 (pegargiminase) and human recombinant pegylated arginases (rhArgPEG, BCT-100 and pegzilarginase). Moreover, recent work has identified an intriguing role for targeting arginine in combination with PD-1/PD-L1 immune checkpoint inhibitors and clinical trials are in progress. Thus, future studies of arginine-depleting agents with chemoimmunotherapy, the current standard of care for SCLC, may lead to enhanced disease control and much needed improvements in long-term survival for patients.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-1 (Programmed cell death 1) • ASS1 (Argininosuccinate synthase 1)
|
Hepacid (pegargiminase) • pegylated recombinant human arginase (BCT-100) • Loargys (pegzilarginase)
over2years
Role of 3'-Deoxy-3'-[F] Fluorothymidine Positron Emission Tomography-Computed Tomography as a Predictive Biomarker in Argininosuccinate Synthetase 1-Deficient Thoracic Cancers Treated With Pegargiminase. (PubMed, JTO Clin Res Rep)
Imaging with proliferation biomarker 3'-deoxy-3'-[F] fluorothymidine (F-FLT) positron emission tomography (PET)-computed tomography (CT) was performed in a phase 1 study of pegargiminase with pemetrexed and cisplatin (ADIPemCis). Both early and late FLT PET-CT provide evidence of response to ADIPemCis therapy in MPM and NSCLC. We provide first-in-human FLT PET-CT data in MPM, indicating it is comparable with modified RECIST.
Journal
|
ASS1 (Argininosuccinate synthase 1)
|
cisplatin • pemetrexed • Hepacid (pegargiminase)
over2years
Mono-PEGylated thermostable Bacillus caldovelox arginase mutant (BCA-M-PEG20) induces apoptosis, autophagy, cell cycle arrest and growth inhibition in gastric cancer cells. (PubMed, Invest New Drugs)
In vivo studies showed that administrations of BCA-M-PEG20 at 250 U/mouse twice per week significantly suppressed about 50% of tumor growth in the MKN-45 gastric cancer xenograft model. Taken together, BCA-M-PEG20 demonstrated a superior potential to be an anti-gastric cancer drug.
Journal
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ASS1 (Argininosuccinate synthase 1) • ARG1 (Arginase 1)
over2years
Invariant NKT cells metabolically adapt to the acute myeloid leukaemia environment. (PubMed, Cancer Immunol Immunother)
The capacity of iNKT cells to restore antigen-specific T cell immunity was similarly demonstrated against myeloid-derived suppressor cells (MDSCs) in wild-type and Jα18 syngeneic lymphoma-bearing models in vivo. Thus, stimulation of iNKT cell activity has the potential as an immunotherapy against AML or as an adjunct to boost antigen-specific T cell immunotherapies in haematological or solid cancers.
Journal • IO biomarker
|
IFNG (Interferon, gamma) • ASS1 (Argininosuccinate synthase 1) • ARG2 (Arginase 2)
over2years
LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells. (PubMed, BMC Cancer)
These results demonstrated that LAP3 mediated IFN-γ-induced arginine depletion to malignant transformation of BMECs. Our findings provide a potential therapeutic target for breast cancer both in humans and dairy cows.
Journal
|
IFNG (Interferon, gamma) • ASS1 (Argininosuccinate synthase 1) • HDAC2 (Histone deacetylase 2) • CCNA1 (Cyclin A1)
|
HDAC2 expression
over2years
Characterisation of Expression the Arginine Pathway Enzymes in Childhood Brain Tumours to Determine Susceptibility to Therapeutic Arginine Depletion. (PubMed, Biomed Res Int)
Pegylated arginase (BCT-100) is currently in phase I/II trials in relapsed pHGG. Our results suggest that therapeutic arginine depletion may also be useful in other tumour types and IHC analysis of patient tumour samples could help identify patients likely to benefit from this treatment.
Journal
|
ASS1 (Argininosuccinate synthase 1) • ARG2 (Arginase 2)
|
pegylated recombinant human arginase (BCT-100)
over2years
Pilot Trial of Arginine Deprivation Plus Nivolumab and Ipilimumab in Patients with Metastatic Uveal Melanoma. (PubMed, Cancers (Basel))
This study aims at investigating the safety and tolerability of a triple combination consisting of ipilimumab and nivolumab immunotherapy and the metabolic therapy, ADI-PEG 20. Further, an IFNg-dependent inflammatory signature was observed in metastatic lesions in patients pre-treated with ICB compared with patients with no pretreatment. Multiplex immunohistochemistry demonstrated variable presence of tumor infiltrating CD8 lymphocytes and PD-L1 expression at the baseline in metastases.
Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • ASS1 (Argininosuccinate synthase 1)
|
PD-L1 expression • TMB-L
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Opdivo (nivolumab) • Yervoy (ipilimumab) • Hepacid (pegargiminase)
over2years
A Phase 1 Study of ADI-PEG20 (Pegargiminase) Combined with Cisplatin and Pemetrexed in ASS1-Negative Metastatic Uveal Melanoma. (PubMed, Pigment Cell Melanoma Res)
ADIPemCis was well tolerated with modest disease stabilisation in metastatic UM. Further investigation of arginine deprivation is indicated in UM including combinations with immune checkpoint blockade and additional antimetabolite strategies.
P1 data • Journal • IO biomarker
|
ASS1 (Argininosuccinate synthase 1)
|
ASS1 negative
|
cisplatin • pemetrexed • Hepacid (pegargiminase)
over2years
Arginine deprivation alters microglia polarity and synergises with radiation to eradicate non arginine auxotrophic glioblastoma tumors. (PubMed, J Clin Invest)
ADI-PEG20 not only enhances the cellular sensitivity of Arginine succinate synthetase 1 positive GBM to ionising radiation by elevated production of nitric oxide (NO) and hence generation of cytotoxic peroxynitrites, but also promotes glioma-associated macrophages/microglia infiltration into tumors and turns their classical anti-inflammatory (pro-tumor) phenotype into a pro-inflammatory (anti-tumor) phenotype. Our results provide an effective, well-tolerated and simple strategy to improve GBM treatment which merits consideration for early evaluation in clinical trials.
Journal
|
ASS1 (Argininosuccinate synthase 1)
almost3years
Pegylated arginase isolated from beef liver tissue inhibited cell proliferation, induced apoptosis & inhibits induced mammary tumors in human breast cancer in vitro & in vivo (AACR 2022)
Furthermore, the results also revealed a significant reduction in activities of ALT, AST, and ALP in the Peg-Arginase group compared to MNU untreated or native-Arginase groups, suggesting that Peg-Arginase may eliminate the hepatotoxic effect of the MNU. All in all, our results suggested that the arginine-depleting enzyme, Peg-Arginase, exerted an anticancer effect against both T-47D and MDA-MB-231 breast cancer cell lines through cell proliferation inhibition and apoptosis induction.
Preclinical
|
TP53 (Tumor protein P53) • CCND1 (Cyclin D1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CASP3 (Caspase 3) • MIR23A (MicroRNA 23a)
|
TP53 mutation • CCND1 mutation
|
pegylated recombinant human arginase (BCT-100)
almost3years
Study of Immunotherapy Plus ADI-PEG 20 for the Treatment of Advanced Uveal Melanoma (clinicaltrials.gov)
P1, N=9, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Apr 2022 --> Apr 2023 | Trial primary completion date: Apr 2022 --> Apr 2023
Trial completion date • Trial primary completion date • Checkpoint inhibition
|
GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11) • CYSLTR2 (Cysteinyl Leukotriene Receptor 2) • PLCB4 (Phospholipase C Beta 4)
|
Opdivo (nivolumab) • Yervoy (ipilimumab) • Hepacid (pegargiminase)
3years
Phase 1 trial of ADI-PEG 20 and liposomal doxorubicin in patients with metastatic solid tumors. (PubMed, Cancer Med)
Concurrent IM injection of ADI-PEG 20 at 36 mg/m weekly and intravenous infusion of PLD at 20 mg/m biweekly had an acceptable safety profile in patients with advanced ASS1-deficient solid tumors. Further evaluation of this combination is under discussion.
Clinical • P1 data • Journal
|
HER-2 (Human epidermal growth factor receptor 2) • ASS1 (Argininosuccinate synthase 1)
|
HER-2 negative
|
Hepacid (pegargiminase)
3years
Priming Death Receptor Mediated Apoptosis with Arginine Starvation Sensitises Arginine Auxotrophic B-ALL to CAR-T (ASH 2021)
Arginine deprivation with the therapeutic enzyme ADI-PEG20 (pegylated arginine deiminase) sensitises cancers deficient in the enzyme argininosuccinate synthase (ASS1) to the apoptosis initiating activity of TRAIL through tumour cell surface upregulation of death receptors DR4 and DR5...Conclusion Our study proposes a synergistic interaction between the arginine depleting enzyme ADI-PEG20 and anti-CD19 CAR-T for the treatment of ASS1 deficient B-ALL, whereby priming of death receptor signalling may underlie enhanced CAR-T cytotoxicity against CD19 + tumour cells. These data support an emerging framework for CAR-T optimisation based on targeting of the death receptor mediated extrinsic apoptosis pathway and can inform future refinements in the development of cellular immunotherapy.
IO biomarker
|
HIF1A (Hypoxia inducible factor 1, alpha subunit) • ASS1 (Argininosuccinate synthase 1) • TNFRSF10B (TNF Receptor Superfamily Member 10b)
|
HIF1A overexpression • HIF1A expression
|
Hepacid (pegargiminase)
3years
Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1-Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms. (PubMed, JTO Clin Res Rep)
The dose expansion of ADIPemCis confirmed the high clinical activity and good tolerability in ASS1-deficient poor-prognosis mesothelioma, underpinning an ongoing phase 3 study (ClinicalTrials.govNCT02709512). Notably, resistance to pegargiminase correlated with marked macrophage recruitment and-along with the tumor immune microenvironment-warrants further study to optimize arginine deprivation for the treatment of mesothelioma.
Clinical • P1 data • Journal • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • ASS1 (Argininosuccinate synthase 1)
|
cisplatin • pemetrexed • Hepacid (pegargiminase)
3years
[VIRTUAL] Preliminary Results of the Phase 2 Portion of the ATOMIC-meso Study Comparing ADI-PEG20 or Placebo with Pemetrexed and Cisplatin in Patients with ASS1-deficient Nonepithelioid Mesothelioma (IMIG 2021)
In the TRAP Phase 1 trial (NCT02029690) ADI-PEG 20 combined with 1st-line pemetrexed (PEM) and cisplatin (CDDP) chemotherapy revealed a 94% disease control rate (34/36) in MPM with a 33.3% partial response rate in biphasic and sarcomatoid subtypes...Patients who developed CDDP toxicity were switched to carboplatin... ATOMIC-meso is the largest first-line triplet chemotherapy study to assess the role of targeted arginine deprivation in aggressive subtypes of mesothelioma on a global scale (US, Europe, and Australasia). The overall blinded data is encouraging and an interim analysis for ORR is planned once the 176 patients have reached the first CT treatment response assessment scan. Pending a Go decision, a total of up to 386 patients will be randomized to complete ATOMIC-meso (NCT02709512).
Clinical • P2 data
|
ASS1 (Argininosuccinate synthase 1)
|
cisplatin • carboplatin • pemetrexed • Hepacid (pegargiminase)
over3years
NEI-01-induced arginine deprivation has potent activity against acute myeloid leukemia cells both in vitro and in vivo. (PubMed, Mol Cancer Ther)
Furthermore, the potent anti-leukemia activities of NEI-01 were observed in three different types of mouse models including human cell line-derived xenograft (CDX), mouse cell line-derived homografts in syngeneic mice and patient-derived xenograft (PDX). This preclinical data provide strong evidence to support the potential use of NEI-01 as a therapeutic approach in AML treatment.
Preclinical • Journal
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ASS1 (Argininosuccinate synthase 1)