ArticleCancer medicine2021
Phase 1, pharmacogenomic, dose-expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1-deficient non-squamous non-small cell lung cancer.
Article in Cancer medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
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- Emerging roles of metabolic biomarkers in renal cell carcinoma: from molecular mechanisms to clinical implications.Frontiers in cell and developmental biology · 2025Review
- Arginine deprivation enriches lung cancer proteomes with cysteine by inducing arginine-to-cysteine substitutants.Molecular cell · 2024Article
- PARC: a phase I/II study evaluating the safety and activity of pegylated recombinant human arginase BCT-100 in relapsed/refractory cancers of children and young adults.Frontiers in oncology · 2024Article
- Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment.International journal of molecular sciences · 2023Review
- Bench-to-Bedside Studies of Arginine Deprivation in Cancer.Molecules (Basel, Switzerland) · 2023Review
- Role of 3'-Deoxy-3'-[JTO clinical and research reports · 2022Article
- Creatine riboside is a cancer cell-derived metabolite associated with arginine auxotrophy.The Journal of clinical investigation · 2022Article
- Arginine Deprivation in SCLC: Mechanisms and Perspectives for Therapy.Lung Cancer (Auckland, N.Z.) · 2022Review
- Argininosuccinate synthase 1, arginine deprivation therapy and cancer management.Frontiers in pharmacology · 2022Review
- PEGylation increases antitumoral activity of arginine deiminase of Streptococcus pyogenes.Applied microbiology and biotechnology · 2022Article
- Phase 1, pharmacogenomic, dose-expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1-deficient non-squamous non-small cell lung cancer.Cancer medicine · 2021Article
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionWe evaluated the arginine-depleting enzyme pegargiminase (ADI-PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1-deficient non-squamous non-small cell lung cancer (NSCLC) via a phase 1 dose-expansion trial with exploratory biomarker analysis.
methodsSixty-seven chemonaïve patients with advanced non-squamous NSCLC were screened, enrolling 21 ASS1-deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m
resultsADIPemCis was well-tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%-97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%-70.2%). The median progression-free and overall survivals were 4.2 (95% CI 2.9-4.8) and 7.2 (95% CI 5.1-18.4) months, respectively. Two PD-L1-expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1-proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD-L1 (<1%) expression (55.6%). Re-expression of tumoral ASS1 was detected in one patient at progression (n = 1/3).
conclusionsADIPemCis was safe and highly active in patients with ASS1-deficient non-squamous NSCLC, however, survival was poor overall. ASS1 loss was co-associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1-deficient and treatment-refractory NSCLC.
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