Evaluation of Safety of Treatment With Anti–Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors

Qiu, Miaozhen; Zhang, Yang; Guo, Ye; Guo, Wei; Nian, Weiqi; Liao, Wangjun; Xu, Zhongyuan; Zhang, Wenxue; Zhao, Hongyun; Wei, Xiaoli; Xue, Lu; Tang, Wenbo; Wu, Yongwei; Ren, Guoxin; Xi, Jingle; Jin, Yongshuai; Li, Hu; Hu, Chaofang; Xu, Rui‐hua

doi:10.1001/jamaoncol.2022.0503

Cited by 21 publications

(14 citation statements)

References 14 publications

(25 reference statements)

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“…Thus, EGFR may serve as a potential prognostic predictor of NPC [ 17 , 37 , 38 ]. A phase 1 nonrandomized clinical trial suggested that MRG003 (an anti-EGFR antibody) showed promising antitumor activity in patients with EGFR-positive NPC [ 39 ]. Other monoclonal antibody drugs targeting EGFR, such as nimotuzumab and cetuximab, also showed satisfactory clinical benefits and a manageable safety profile for advanced or recurrent/metastatic NPC [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma

Fei

Hong

et al. 2023

Radiat Oncol

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Objective This study inventively combines epidermal growth factor receptor (EGFR) expression of the primary lesion and standardized uptake value (SUV) of positron emission tomography and computed tomography (PET/CT) to predict the prognosis of nasopharyngeal carcinoma (NPC). This study aimed to evaluate the predictive efficacy of maximum standard uptake value (SUVmax) and EGFR for treatment failure in patients with NPC. Methods This retrospective study reviewed the results of EGFR expression and pretreatment 18F-FDG PET/CT of 313 patients with NPC. Time-dependent receiver operator characteristics was used for analyzing results and selecting the optimal cutoff values. Cox regression was used to screen out multiple risk factors. Cumulative survival rate was calculated by Kaplan–Meier. Results The selected cutoff value of SUVmax-T was 8.5. The patients were categorized into four groups according to EGFR expression and SUVmax-T. There were significant differences in the 3-year local recurrence-free survival (LRFS) (p = 0.0083), locoregional relapse-free survival (LRRFS) (p = 0.0077), distant metastasis-free survival (DMFS) (p = 0.013), and progression-free survival (PFS) (p = 0.0018) among the four groups. Patients in the EGFR-positive and SUVmax-T > 8.5 group had the worst survival, while patients in the EGFR-negative and SUVmax-T ≤ 8.5 group had the best prognosis. Subsequently, patients with only positive EGFR expression or high SUVmax-T were classified as the middle-risk group. There were also a significant difference in 3-year overall survival among the three risk groups (p = 0.034). SUVmax-T was associated with regional recurrence-free survival and LRRFS in multivariate analysis, whereas EGFR was an independent prognostic factor for LRRFS, DMFS, and PFS. Conclusion The combination of SUVmax-T and EGFR expression can refine prognosis and indicate clinical therapy.

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Section: Discussionmentioning

confidence: 99%

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma

Fei

Hong

et al. 2023

Radiat Oncol

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“…132 The MRG003 ADC consists of an anti-EGFR mAb conjugated to MMAE via a cleavable linker, and is under evaluation in a phase II trial in patients with pretreated EGFR-mutant NSCLC (ClinicalTrials.gov identifier: NCT04838548). 133 ROR2, a transmembrane receptor interacting with the noncanonical Wnt pathway, is also frequently expressed in several tumors including NSCLC, 135 and trials are currently ongoing to evaluate ROR2-targeted ADC (BA3021).Sodium-dependent phosphate transporter type II (NaPi2b) was found highly expressed in about 70% of NSCLC. 136 Upifitamab rilsodotin (XMT-1536) and lifastuzumab vedotin are NaPi2b-directed ADCs currently investigated in clinical trials in NSCLC.…”

Section: Carcinoembryonic Antigen–related Cell Adhesion Moleculementioning

confidence: 99%

Section: Carcinoembryonic Antigen–related Cell Adhesion Moleculementioning

confidence: 99%

Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies

Passaro

Peters

2023

JCO

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Antibody-drug conjugates (ADCs) are one of the fastest-growing oncology therapeutics, merging the cytotoxic effect of conjugated payload with the high specific ability and selectivity of monoclonal antibody targeted on a specific cancer cell membrane antigen. The main targets for ADC development are antigens commonly expressed by lung cancer cells, but not in normal tissues. They include human epidermal growth factor receptor 2, human epidermal growth factor receptor 3, trophoblast cell surface antigen 2, c-MET, carcinoembryonic antigen–related cell adhesion molecule 5, and B7-H3, each with one or more specific ADCs that showed encouraging results in the lung cancer field, more in non–small-cell lung cancer than in small-cell lung cancer histology. To date, multiple ADCs are under evaluation, alone or in combination with different molecules (eg, chemotherapy agents or immune checkpoint inhibitors), and the optimal strategy for selecting patients who may benefit from the treatment is evolving, including an improvement of biomarker understanding, involving markers of resistance or response to the payload, besides the antibody target. In this review, we discuss the available evidence and future perspectives on ADCs for lung cancer treatment, including a comprehensive discussion on structure-based drug design, mechanism of action, and resistance concepts. Data were summarized by specific target antigen, biology, efficacy, and safety, differing among ADCs according to the ADC payload and their pharmacokinetics and pharmacodynamics properties.

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“…MRG003 is a new ADC containing an anti-EGFR IgG1 mAb connected to monomethyl auristatin E by a cleavable linker. 57 Another ADC targeting EGFR is depatuxizumab mafodotin (Depatux-M). This ADC contains a humanized recombinant IgG that binds to EGFR, a noncleavable maleimidocaproyl linker, and monomethyl auristatin F. Depatux-M was developed to target EGFR variant III-expressing cells because this EGFR's variant is more frequently expressed in tumor cells.…”

Section: Egfrmentioning

confidence: 99%

“…In the past year, 2 ADCs targeting EGFR were evaluated in clinical trials. MRG003 is a new ADC containing an anti-EGFR IgG1 mAb connected to monomethyl auristatin E by a cleavable linker 57 . Another ADC targeting EGFR is depatuxizumab mafodotin (Depatux-M).…”

Section: Egfrmentioning

confidence: 99%

Antibody-Drug Conjugates and Tissue-Agnostic Drug Development

2022

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Antibody-drug conjugates (ADCs) deliver effective medications to tumor cells that express specific antigens, maximizing efficacy and reducing adverse effects. Because ado-trastuzumab emtansine was approved in 2013, 5 ADCs received US Food and Drug Administration approval for solid tumor treatment. Technical advancements in the development of each component of ADCs allowed novel monoclonal antibodies, linkers, and payloads to increase drug transport to malignant cells and drug activity even in cancers with heterogeneous antigen expression. In addition, several ADCs are in development using new molecular targets expressed across a broad range of histologies to allow the use of ADC biomarker-driven therapy irrespective of the primary tumor site. This suggests that the future efficacy of ADCs in multiple histologies may be similar to other classes of drugs that are considered histology-agnostic therapies nowadays. This review focuses on novel ADCs for the treatment of solid tumors, including topics such as their structure and mechanism of action, the latest indications of already US Food and Drug Administration-approved ADCs, and the outlook for new promising ADCs under development for the treatment of tumors of various histologies.

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Evaluation of Safety of Treatment With Anti–Epidermal Growth Factor Receptor Antibody Drug Conjugate MRG003 in Patients With Advanced Solid Tumors

Cited by 21 publications

References 14 publications

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma

PET/CT standardized uptake value and EGFR expression predicts treatment failure in nasopharyngeal carcinoma

Antibody-Drug Conjugates in Lung Cancer: Recent Advances and Implementing Strategies

Antibody-Drug Conjugates and Tissue-Agnostic Drug Development

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