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Article ; Online: Erratum: Drug Discovery Approaches to Target Wnt Signaling in Cancer Stem Cells.

Curtin, Joshua C / Lorenzi, Matthew V

2018 Volume 9, Issue 78, Page(s) 34856

Abstract: This corrects the article DOI: 10.18632/oncotarget.191.]. ...

Abstract	[This corrects the article DOI: 10.18632/oncotarget.191.].
Language	English
Publishing date	2018-10-05
Publishing country	United States
Document type	Journal Article ; Published Erratum
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.26220
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Article ; Online: Ageing attenuates exercise-enhanced motor cortical plasticity.

Curtin, Dylan / Cadwallader, Claire J / Taylor, Eleanor M / Andrews, Sophie C / Stout, Julie C / Hendrikse, Joshua J / Chong, Trevor T-J / Coxon, James P

The Journal of physiology

2023 Volume 601, Issue 24, Page(s) 5733–5750

Abstract: Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical ... ...

Abstract	Cardiorespiratory exercise is known to modulate motor cortical plasticity in young adults, but the influence of ageing on this relationship is unknown. Here, we compared the effects of a single session of cardiorespiratory exercise on motor cortical plasticity in young and older adults. We acquired measures of cortical excitatory and inhibitory activity of the primary motor cortex using transcranial magnetic stimulation (TMS) from 20 young (mean ± SD = 25.30 ± 4.00 years, 14 females) and 20 older (mean ± SD = 64.10 ± 6.50 years, 11 females) healthy adults. Single- and paired-pulse TMS measurements were collected before and after a 20 min bout of high-intensity interval cycling exercise or an equivalent period of rest, and again after intermittent theta burst stimulation (iTBS). In both young (P = 0.027, Cohen's d = 0.87) and older adults (P = 0.006, Cohen's d = 0.85), there was an increase in glutamatergic excitation and a reduction in GABAergic inhibition from pre- to postexercise. However, in contrast to younger adults, older adults showed an attenuated plasticity response to iTBS following exercise (P = 0.011, Cohen's d = 0.85). These results demonstrate an age-dependent decline in cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults. Our findings align with the hypothesis that the capacity for cortical plasticity is altered in older age. KEY POINTS: Exercise enhances motor cortical plasticity in young adults, but how ageing influences this effect is unknown. Here, we compared primary motor cortical plasticity responses in young and older adults before and after a bout of high-intensity interval exercise and again after a plasticity-inducing protocol, intermittent theta burst stimulation. In both young and older adults, exercise led to an increase in glutamatergic excitation and a reduction in GABAergic inhibition. Our key result was that older adults showed an attenuated plasticity response to theta burst stimulation following exercise, relative to younger adults. Our findings demonstrate an age-dependent decline in exercise-enhanced cortical plasticity and indicate that a preceding bout of high-intensity interval exercise might be less effective for enhancing primary motor cortex plasticity in older adults.
MeSH term(s)	Female ; Young Adult ; Humans ; Aged ; Neuronal Plasticity/physiology ; Motor Cortex/physiology ; Evoked Potentials, Motor/physiology ; Transcranial Magnetic Stimulation/methods ; Aging
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Journal Article
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/JP285243
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Article ; Online: Novel drug discovery opportunities for colorectal cancer.

Curtin, Joshua C

Expert opinion on drug discovery

2013 Volume 8, Issue 9, Page(s) 1153–1164

Abstract: Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with > 1.2 million new cases and > 600,000 deaths per year. This complex disease is driven by multiple genetic lesions, commonly dysregulated signaling pathways, and ...

Abstract	Introduction: Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide, with > 1.2 million new cases and > 600,000 deaths per year. This complex disease is driven by multiple genetic lesions, commonly dysregulated signaling pathways, and aberrant activity of developmental programs such as Notch and Wnt. While emerging therapies such as EGFR inhibitors are improving treatment regimens, recent findings elucidating the role of cancer stem cells provide insights into opportunities for novel therapeutic intervention. Areas covered: This review provides a background on CRC statistics, colon anatomy and CRC pathobiology, CRC genetics and current and emerging therapies. Furthermore, the article discusses the role of developmental signaling pathways governing self-renewal biology as potential points for therapeutic intervention. Expert opinion: Despite recent advances including the introduction of targeted therapeutics, prognosis for advanced CRC patients remains bleak, reinforcing the need for novel therapeutic intervention. Developmental pathways such as Notch and Wnt provide opportunities to address this urgent need, and preclinical evidence supports targeting these pathways in CRC. Progress has been made toward this end, and while challenges persist, an increasing number of preclinical findings show promise.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Drug Discovery ; Humans ; Neoplastic Stem Cells
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2013-09
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2259618-5
ISSN	1746-045X ; 1746-0441
ISSN (online)	1746-045X
ISSN	1746-0441
DOI	10.1517/17460441.2013.807249
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Zs.A 6388: Show issues

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Article ; Online: Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study.

Park, Keunchil / Sabari, Joshua K / Haura, Eric B / Shu, Catherine A / Spira, Alexander / Salgia, Ravi / Reckamp, Karen L / Sanborn, Rachel E / Govindan, Ramaswamy / Bauml, Joshua M / Curtin, Joshua C / Xie, John / Roshak, Amy / Lorenzini, Patricia / Millington, Dawn / Thayu, Meena / Knoblauch, Roland E / Cho, Byoung Chul

Lung cancer (Amsterdam, Netherlands)

2023 Volume 178, Page(s) 166–171

Abstract: Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related ... ...

Abstract	Background: Amivantamab, a fully humanized EGFR-MET bispecific antibody, has antitumor activity in diverse EGFR- and MET-driven non-small cell lung cancer (NSCLC) and a safety profile consistent with associated on-target activities. Infusion-related reaction(s) (IRR[s]) are reported commonly with amivantamab. We review IRR and subsequent management in amivantamab-treated patients. Methods: Patients treated with the approved dose of intravenous amivantamab (1050 mg, <80 kg; 1400 mg, ≥80 kg) in CHRYSALIS-an ongoing, phase 1 study in advanced EGFR-mutated NSCLC-were included in this analysis. IRR mitigations included split first dose (350 mg, day 1 [D1]; remainder, D2), reduced initial infusion rates with proactive infusion interruption, and steroid premedication before initial dose. For all doses, pre-infusion antihistamines and antipyretics were required. Steroids were optional after the initial dose. Results: As of 3/30/2021, 380 patients received amivantamab. IRRs were reported in 256 (67%) patients. Signs/symptoms of IRR included chills, dyspnea, flushing, nausea, chest discomfort, and vomiting. Most of the 279 IRRs were grade 1 or 2; grade 3 and 4 IRR occurred in 7 and 1 patients, respectively. Most (90%) IRRs occurred on cycle 1, D1 (C1D1); median time-to-first-IRR onset during C1D1 was 60 min; and first-infusion IRRs did not compromise subsequent infusions. Per protocol, IRR was mitigated on C1D1 with holding of infusion (56% [214/380]), reinitiating at reduced rate (53% [202/380]), and aborting infusion (14% [53/380]). C1D2 infusions were completed in 85% (45/53) of patients who had C1D1 infusions aborted. Four patients (1% [4/380]) discontinued treatment due to IRR. In studies aimed at elucidating the underlying mechanism(s) of IRR, no pattern was observed between patients with versus without IRR. Conclusion: IRRs with amivantamab were predominantly low grade and limited to first infusion, and rarely occurred with subsequent dosing. Close monitoring for IRR with the initial amivantamab dose and early intervention at first IRR signs/symptoms should be part of routine amivantamab administration.
MeSH term(s)	Animals ; Humans ; Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Drug-Related Side Effects and Adverse Reactions ; ErbB Receptors ; Immune System Diseases ; Lung Neoplasms ; Pupa
Chemical Substances	amivantamab-vmjw ; Antibodies, Bispecific ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2023-02-15
Publishing country	Ireland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2023.02.008
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Frequency, underdiagnosis, and heterogeneity of epidermal growth factor receptor exon 20 insertion mutations using real-world genomic datasets.

Viteri, Santiago / Minchom, Anna / Bazhenova, Lyudmila / Ou, Sai-Hong Ignatius / Bauml, Joshua M / Shell, Scott A / Schaffer, Michael / Gu, Junchen / Rose, Jennifer B / Curtin, Joshua C / Mahadevia, Parthiv / Girard, Nicolas

Molecular oncology

2022 Volume 17, Issue 2, Page(s) 230–237

Abstract: Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR-mutant nonsmall cell lung cancers. We analysed real-world datasets to determine the frequency of ex20ins variants, and the ability of polymerase ... ...

Abstract	Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (ex20ins) account for ≤ 12% of all EGFR-mutant nonsmall cell lung cancers. We analysed real-world datasets to determine the frequency of ex20ins variants, and the ability of polymerase chain reaction (PCR) and next-generation sequencing (NGS) to identify them. Three real-world United States NGS databases were used: GENIE, FoundationInsights, and GuardantINFORM. Mutation profiles consistent with in-frame EGFR ex20ins were summarized. GENIE, FoundationInsights, and GuardantINFORM datasets identified 180, 627, and 627 patients with EGFR ex20ins respectively. The most frequent insertion region of exon 20 was the near loop (~ 70%), followed by the far loop (~ 30%) and the helical (~ 3-6%) regions. GENIE, FoundationInsights, and GuardantINFORM datasets identified 41, 102, and 96 unique variants respectively. An analysis of variants projected that ~ 50% of EGFR ex20ins identified by NGS would have been missed by PCR-based assays. Given the breadth of EGFR ex20ins identified in the real-world US datasets, the ability of PCR to identify these mutations is limited. NGS platforms are more appropriate to identify patients likely to benefit from EGFR ex20ins-targeted therapies.
MeSH term(s)	Humans ; Lung Neoplasms/diagnosis ; Lung Neoplasms/genetics ; Mutagenesis, Insertional/genetics ; ErbB Receptors/genetics ; Mutation/genetics ; Exons/genetics ; Genomics ; Protein Kinase Inhibitors
Chemical Substances	ErbB Receptors (EC 2.7.10.1) ; Protein Kinase Inhibitors
Language	English
Publishing date	2022-11-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13327
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Article ; Online: Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial.

Nature medicine

2023 Volume 29, Issue 10, Page(s) 2577–2585

Abstract: Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib- ... ...

Abstract	Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776 .
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Prospective Studies ; Protein Kinase Inhibitors/therapeutic use ; Protein Kinase Inhibitors/pharmacology ; Mutation/genetics ; Aniline Compounds/therapeutic use ; ErbB Receptors/genetics
Chemical Substances	osimertinib (3C06JJ0Z2O) ; lazertinib (4A2Y23XK11) ; amivantamab-vmjw ; Protein Kinase Inhibitors ; Aniline Compounds ; ErbB Receptors (EC 2.7.10.1) ; EGFR protein, human (EC 2.7.10.1)
Language	English
Publishing date	2023-09-14
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02554-7
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Drug discovery approaches to target Wnt signaling in cancer stem cells.

Curtin, Joshua C / Lorenzi, Matthew V

Oncotarget

2014 Volume 1, Issue 7, Page(s) 563–577

Abstract: Cancer stem cells (CSCs) represent a unique subset of cells within a tumor that possess self-renewal capacity and pluripotency, and can drive tumor initiation and maintenance. First identified in hematological malignancies, CSCs are now thought to play ... ...

Abstract	Cancer stem cells (CSCs) represent a unique subset of cells within a tumor that possess self-renewal capacity and pluripotency, and can drive tumor initiation and maintenance. First identified in hematological malignancies, CSCs are now thought to play an important role in a wide variety of solid tumors such as NSCLC, breast and colorectal cancer. The role of CSCs in driving tumor formation illustrates the dysregulation of differentiation in tumorigenesis. The Wnt, Notch and Hedgehog (HH) pathways are developmental pathways that are commonly activated in many types of cancer. While substantial progress has been made in developing therapeutics targeting Notch and HH, the Wnt pathway has remained an elusive therapeutic target. This review will focus on the clinical relevance of the Wnt pathway in CSCs and tumor cell biology, as well as points of therapeutic intervention and recent advances in targeting Wnt/β-catenin signaling.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Drug Discovery/methods ; Humans ; Molecular Targeted Therapy/methods ; Neoplasms/drug therapy ; Neoplasms/pathology ; Neoplastic Stem Cells/drug effects ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Signal Transduction/drug effects ; Signal Transduction/genetics ; Wnt Proteins/antagonists & inhibitors ; Wnt Proteins/metabolism ; Wnt Proteins/physiology
Chemical Substances	Antineoplastic Agents ; Wnt Proteins
Language	English
Publishing date	2014-07-11
Publishing country	United States
Document type	Evaluation Study ; Journal Article ; Review
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.191
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Article ; Online: Clinical Validation of Companion Diagnostics for the Selection of Patients with Non-Small Cell Lung Cancer Tumors Harboring Epidermal Growth Factor Receptor Exon 20 Insertion Mutations for Treatment with Amivantamab.

Jatkoe, Timothy / Wang, Songbai / Odegaard, Justin I / Velasco Roth, Anne Marie / Osgood, Drew / Martinez, Gabriela / Lucas, Paul / Curtin, Joshua C / Karkera, Jayaprakash

The Journal of molecular diagnostics : JMD

2022 Volume 24, Issue 11, Page(s) 1181–1188

Abstract: Amivantamab, an epidermal growth factor receptor (EGFR)-c-Met bispecific antibody, targets ...

Abstract	Amivantamab, an epidermal growth factor receptor (EGFR)-c-Met bispecific antibody, targets activating/resistance EGFR mutations and MET mutations/amplifications. In the ongoing CHRYSALIS study (ClinicalTrials.gov Identifier: NCT02609776), amivantamab demonstrated antitumor activity in patients with non-small cell lung cancer harboring EGFR exon 20 insertion mutations (ex20ins) that progressed on or after platinum-based chemotherapy, a population in which amivantamab use has been approved by the US Food and Drug Administration. This bridging study clinically validated two novel candidate companion diagnostics (CDx) for use in detecting EGFR ex20ins in plasma and tumor tissue, Guardant360 CDx and Oncomine Dx Target Test (ODxT), respectively. From the 81 patients in the CHRYSALIS efficacy population, 78 plasma and 51 tissue samples were tested. Guardant360 CDx identified 62 positive (16 negative), and ODxT identified 39 positive (3 negative), samples with EGFR ex20ins. Baseline demographic and clinical characteristics were similar between the CHRYSALIS-, Guardant360 CDx-, and ODxT-identified populations. Agreement with local PCR/next-generation sequencing tests used for enrollment into CHRYSALIS demonstrated high adjusted negative (99.6% and 99.9%) and positive (100% for both) predictive values with the Guardant360 CDx and ODxT tests, respectively. Overall response rates were comparable between the CHRYSALIS, Guardant360 CDx, and ODxT populations. Both the plasma- and tissue-based diagnostic tests provided accurate, comprehensive, and complementary approaches to identifying patients with EGFR ex20ins who could benefit from amivantamab therapy.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/diagnosis ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Patient Selection ; Mutagenesis, Insertional/genetics ; Protein Kinase Inhibitors/therapeutic use ; ErbB Receptors/genetics ; Exons/genetics ; Mutation
Chemical Substances	amivantamab-vmjw ; Protein Kinase Inhibitors ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2022-08-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2000060-1
ISSN	1943-7811 ; 1525-1578
ISSN (online)	1943-7811
ISSN	1525-1578
DOI	10.1016/j.jmoldx.2022.07.003
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Article: Image-based models of T-cell distribution identify a clinically meaningful response to a dendritic cell vaccine in patients with glioblastoma.

medRxiv : the preprint server for health sciences

2023

Abstract: Background: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but ...

Abstract	Background: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity. Methods: Using an image-based modeling approach, we predicted T-cell abundance from serial MRIs of patients enrolled in the dendritic cell (DC) vaccine clinical trial. T-cell predictions were quantified in both the contrast-enhancing and non-enhancing regions of the imageable tumor, and changes over time were assessed. Results: A subset of patients in a DC vaccine clinical trial, who had previously gone undetected, were identified as treatment responsive and benefited from prolonged survival. A mere two months after initial vaccine administration, responsive patients had a decrease in model-predicted T-cells within the contrast-enhancing region, with a simultaneous increase in the T2/FLAIR region. Conclusions: In a field that has yet to see breakthrough therapies, these results highlight the value of machine learning in enhancing clinical trial assessment, improving our ability to prospectively prognosticate patient outcomes, and advancing the pursuit towards individualized medicine.
Language	English
Publishing date	2023-07-16
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.07.13.23292619
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Article ; Online: Amivantamab in EGFR Exon 20 Insertion-Mutated Non-Small-Cell Lung Cancer Progressing on Platinum Chemotherapy: Initial Results From the CHRYSALIS Phase I Study.

Park, Keunchil / Haura, Eric B / Leighl, Natasha B / Mitchell, Paul / Shu, Catherine A / Girard, Nicolas / Viteri, Santiago / Han, Ji-Youn / Kim, Sang-We / Lee, Chee Khoon / Sabari, Joshua K / Spira, Alexander I / Yang, Tsung-Ying / Kim, Dong-Wan / Lee, Ki Hyeong / Sanborn, Rachel E / Trigo, José / Goto, Koichi / Lee, Jong-Seok /

Yang, James Chih-Hsin / Govindan, Ramaswamy / Bauml, Joshua M / Garrido, Pilar / Krebs, Matthew G / Reckamp, Karen L / Xie, John / Curtin, Joshua C / Haddish-Berhane, Nahor / Roshak, Amy / Millington, Dawn / Lorenzini, Patricia / Thayu, Meena / Knoblauch, Roland E / Cho, Byoung Chul

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2021 Volume 39, Issue 30, Page(s) 3391–3402

Abstract: Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (: Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with : Results: In the efficacy population (n = ...

Abstract	Purpose: Non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor ( Methods: CHRYSALIS is a phase I, open-label, dose-escalation, and dose-expansion study, which included a population with Results: In the efficacy population (n = 81), the median age was 62 years (range, 42-84 years); 40 patients (49%) were Asian, and the median number of previous lines of therapy was two (range, 1-7). The overall response rate was 40% (95% CI, 29 to 51), including three complete responses, with a median duration of response of 11.1 months (95% CI, 6.9 to not reached). The median progression-free survival was 8.3 months (95% CI, 6.5 to 10.9). In the safety population (n = 114), the most common adverse events were rash in 98 patients (86%), infusion-related reactions in 75 (66%), and paronychia in 51 (45%). The most common grade 3-4 adverse events were hypokalemia in six patients (5%) and rash, pulmonary embolism, diarrhea, and neutropenia in four (4%) each. Treatment-related dose reductions and discontinuations were reported in 13% and 4% of patients, respectively. Conclusion: Amivantamab, via its novel mechanism of action, yielded robust and durable responses with tolerable safety in patients with
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Antibodies, Bispecific/administration & dosage ; Antibodies, Bispecific/adverse effects ; Antibodies, Bispecific/pharmacokinetics ; Antineoplastic Agents, Immunological/administration & dosage ; Antineoplastic Agents, Immunological/adverse effects ; Antineoplastic Agents, Immunological/pharmacokinetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/secondary ; Diarrhea/chemically induced ; Disease Progression ; Drug Eruptions/etiology ; ErbB Receptors/genetics ; Exons ; Female ; Humans ; Hypokalemia/chemically induced ; Injection Site Reaction/etiology ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Male ; Middle Aged ; Mutagenesis, Insertional ; Neutropenia/chemically induced ; Organoplatinum Compounds/therapeutic use ; Paronychia/chemically induced ; Progression-Free Survival ; Pulmonary Embolism/chemically induced ; Retreatment
Chemical Substances	Antibodies, Bispecific ; Antineoplastic Agents, Immunological ; Organoplatinum Compounds ; amivantamab-vmjw ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2021-08-02
Publishing country	United States
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.21.00662
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Inter-library loan at ZB MED

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In stock of ZB MED Cologne/Königswinter

Order via subito