Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer

Introduction We 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. Methods Sixty‐seven c...

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Published inCancer medicine (Malden, MA) Vol. 10; no. 19; pp. 6642 - 6652
Main Authors Szlosarek, Peter W., Wimalasingham, Akhila G., Phillips, Melissa M., Hall, Peter E., Chan, Pui Ying, Conibear, John, Lim, Louise, Rashid, Sukaina, Steele, Jeremy, Wells, Paula, Shiu, Chiung‐Fang, Kuo, Chih‐Ling, Feng, Xiaoxing, Johnston, Amanda, Bomalaski, John, Ellis, Stephen, Grantham, Marianne, Sheaff, Michael
Format Journal Article
LanguageEnglish
Published United States John Wiley & Sons, Inc 01.10.2021
John Wiley and Sons Inc
Wiley
Subjects
ADIPemCis
Adult
Aged
arginine
arginine deiminase
ASS1
Biomarkers
Cancer therapies
Carcinoma, Non-Small-Cell Lung - drug therapy
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cisplatin - therapeutic use
Citrulline
Clinical Cancer Research
Cohort Studies
Disease control
Female
Humans
Hydrolases - pharmacology
Hydrolases - therapeutic use
Immunogenicity
Immunohistochemistry
Immunotherapy
Kinases
KRAS
Lung cancer
Lung Neoplasms - drug therapy
Male
Medical prognosis
Mesothelioma
Metastasis
Middle Aged
Monoclonal antibodies
Mutation
Non-small cell lung carcinoma
non‐squamous NSCLC
p53
p53 Protein
Patients
PD-L1 protein
PD‐L1
Pembrolizumab
Pemetrexed - pharmacology
Pemetrexed - therapeutic use
Pharmacodynamics
Pharmacogenomics
Polyethylene Glycols - pharmacology
Polyethylene Glycols - therapeutic use
Response rates
Small cell lung carcinoma
Tumors
arginine deiminase
arginine
non-squamous NSCLC
ADIPemCis
PD-L1
KRAS
ASS1
p53
Online AccessGet full text
ISSN2045-7634
2045-7634
DOI10.1002/cam4.4196

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Abstract Introduction We 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. Methods Sixty‐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/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry. Results ADIPemCis 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). Conclusions ADIPemCis 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. We 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. ADIPemCis 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 providing a developmental pathway for further testing pegargiminase in ASS1‐deficient and treatment‐refractory NSCLC.
AbstractList 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/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry.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.
We 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.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.Sixty-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/m2 ) with Pem (500 mg/m2 ) and Cis (75 mg/m2 ), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry.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/m2 ) with Pem (500 mg/m2 ) and Cis (75 mg/m2 ), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry.ADIPemCis 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).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).ADIPemCis 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.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.
Introduction We 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. Methods Sixty‐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/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry. Results ADIPemCis 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). Conclusions ADIPemCis 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. We 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. ADIPemCis 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 providing a developmental pathway for further testing pegargiminase in ASS1‐deficient and treatment‐refractory NSCLC.
Abstract Introduction We 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. Methods Sixty‐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/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry. Results ADIPemCis 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). Conclusions ADIPemCis 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.
We 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. Sixty-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 ) with Pem (500 mg/m ) and Cis (75 mg/m ), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next-generation sequencing and PD-L1 immunohistochemistry. ADIPemCis 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). ADIPemCis 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.
We 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. ADIPemCis 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 providing a developmental pathway for further testing pegargiminase in ASS1‐deficient and treatment‐refractory NSCLC.
Author Johnston, Amanda
Hall, Peter E.
Grantham, Marianne
Lim, Louise
Ellis, Stephen
Rashid, Sukaina
Steele, Jeremy
Chan, Pui Ying
Phillips, Melissa M.
Bomalaski, John
Conibear, John
Kuo, Chih‐Ling
Feng, Xiaoxing
Sheaff, Michael
Wimalasingham, Akhila G.
Shiu, Chiung‐Fang
Szlosarek, Peter W.
Wells, Paula
AuthorAffiliation 5 Department of Diagnostic Imaging Barts Health NHS Trust St Bartholomew’s Hospital London UK
6 Cytogenetics and Molecular Haematology, Pathology and Pharmacy Building Barts Health NHS Trust Royal London Hospital London UK
1 Center for Cancer Biomarkers and Biotherapeutics Barts Cancer Institute (BCI) – A Cancer Research UK Center of Excellence Queen Mary University of London John Vane Science Center London UK
3 Department of Clinical Oncology Barts Health NHS Trust St Bartholomew’s Hospital London UK
4 Polaris Pharmaceuticals, Inc. San Diego California USA
2 Department of Medical Oncology Barts Health NHS Trust St Bartholomew’s Hospital London UK
7 Department of Histopathology, Pathology and Pharmacy Building Barts Health NHS Trust Royal London Hospital London UK
AuthorAffiliation_xml – name: 5 Department of Diagnostic Imaging Barts Health NHS Trust St Bartholomew’s Hospital London UK
– name: 1 Center for Cancer Biomarkers and Biotherapeutics Barts Cancer Institute (BCI) – A Cancer Research UK Center of Excellence Queen Mary University of London John Vane Science Center London UK
– name: 4 Polaris Pharmaceuticals, Inc. San Diego California USA
– name: 6 Cytogenetics and Molecular Haematology, Pathology and Pharmacy Building Barts Health NHS Trust Royal London Hospital London UK
– name: 2 Department of Medical Oncology Barts Health NHS Trust St Bartholomew’s Hospital London UK
– name: 7 Department of Histopathology, Pathology and Pharmacy Building Barts Health NHS Trust Royal London Hospital London UK
– name: 3 Department of Clinical Oncology Barts Health NHS Trust St Bartholomew’s Hospital London UK
Author_xml – sequence: 1
  givenname: Peter W.
  orcidid: 0000-0002-5039-711X
  surname: Szlosarek
  fullname: Szlosarek, Peter W.
  email: p.w.szlosarek@qmul.ac.uk
  organization: St Bartholomew’s Hospital
– sequence: 2
  givenname: Akhila G.
  surname: Wimalasingham
  fullname: Wimalasingham, Akhila G.
  organization: St Bartholomew’s Hospital
– sequence: 3
  givenname: Melissa M.
  surname: Phillips
  fullname: Phillips, Melissa M.
  organization: St Bartholomew’s Hospital
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  surname: Hall
  fullname: Hall, Peter E.
  organization: St Bartholomew’s Hospital
– sequence: 5
  givenname: Pui Ying
  surname: Chan
  fullname: Chan, Pui Ying
  organization: St Bartholomew’s Hospital
– sequence: 6
  givenname: John
  surname: Conibear
  fullname: Conibear, John
  organization: St Bartholomew’s Hospital
– sequence: 7
  givenname: Louise
  surname: Lim
  fullname: Lim, Louise
  organization: St Bartholomew’s Hospital
– sequence: 8
  givenname: Sukaina
  surname: Rashid
  fullname: Rashid, Sukaina
  organization: St Bartholomew’s Hospital
– sequence: 9
  givenname: Jeremy
  surname: Steele
  fullname: Steele, Jeremy
  organization: St Bartholomew’s Hospital
– sequence: 10
  givenname: Paula
  surname: Wells
  fullname: Wells, Paula
  organization: St Bartholomew’s Hospital
– sequence: 11
  givenname: Chiung‐Fang
  surname: Shiu
  fullname: Shiu, Chiung‐Fang
  organization: Polaris Pharmaceuticals, Inc
– sequence: 12
  givenname: Chih‐Ling
  surname: Kuo
  fullname: Kuo, Chih‐Ling
  organization: Polaris Pharmaceuticals, Inc
– sequence: 13
  givenname: Xiaoxing
  surname: Feng
  fullname: Feng, Xiaoxing
  organization: Polaris Pharmaceuticals, Inc
– sequence: 14
  givenname: Amanda
  surname: Johnston
  fullname: Johnston, Amanda
  organization: Polaris Pharmaceuticals, Inc
– sequence: 15
  givenname: John
  surname: Bomalaski
  fullname: Bomalaski, John
  organization: Polaris Pharmaceuticals, Inc
– sequence: 16
  givenname: Stephen
  surname: Ellis
  fullname: Ellis, Stephen
  organization: St Bartholomew’s Hospital
– sequence: 17
  givenname: Marianne
  surname: Grantham
  fullname: Grantham, Marianne
  organization: Royal London Hospital
– sequence: 18
  givenname: Michael
  surname: Sheaff
  fullname: Sheaff, Michael
  organization: Royal London Hospital
BackLink https://www.ncbi.nlm.nih.gov/pubmed/34382365$$D View this record in MEDLINE/PubMed
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2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Copyright_xml – notice: 2021 The Authors. published by John Wiley & Sons Ltd.
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Keywords arginine deiminase
arginine
non-squamous NSCLC
ADIPemCis
PD-L1
KRAS
ASS1
p53
Language English
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2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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Snippet Introduction We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient...
We evaluated the arginine-depleting enzyme pegargiminase (ADI-PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1-deficient non-squamous...
IntroductionWe evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient...
We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient non‐squamous...
Abstract Introduction We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in...
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SubjectTerms ADIPemCis
Adult
Aged
arginine
arginine deiminase
ASS1
Biomarkers
Cancer therapies
Carcinoma, Non-Small-Cell Lung - drug therapy
Chemotherapy
Cisplatin
Cisplatin - pharmacology
Cisplatin - therapeutic use
Citrulline
Clinical Cancer Research
Cohort Studies
Disease control
Female
Humans
Hydrolases - pharmacology
Hydrolases - therapeutic use
Immunogenicity
Immunohistochemistry
Immunotherapy
Kinases
KRAS
Lung cancer
Lung Neoplasms - drug therapy
Male
Medical prognosis
Mesothelioma
Metastasis
Middle Aged
Monoclonal antibodies
Mutation
Non-small cell lung carcinoma
non‐squamous NSCLC
p53
p53 Protein
Patients
PD-L1 protein
PD‐L1
Pembrolizumab
Pemetrexed - pharmacology
Pemetrexed - therapeutic use
Pharmacodynamics
Pharmacogenomics
Polyethylene Glycols - pharmacology
Polyethylene Glycols - therapeutic use
Response rates
Small cell lung carcinoma
Tumors
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Title Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer
URI https://onlinelibrary.wiley.com/doi/abs/10.1002%2Fcam4.4196
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Volume 10
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