eCase - <em>NRG1</em> Fusion–Positive Tumors: Module

CME

Neuregulin-1 (NRG1): An Emerging Tumor-Agnostic Target

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: February 02, 2022

Expiration: February 01, 2023

Ryma Benayed, PhD

Stephen Liu, MD

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NRG1: An Emerging Tumor-Agnostic Target References

References

Jones MR, Lim H, Shen Y, et al. Successful targeting of the NRG1 pathway indicates novel treatment strategy for metastatic cancer. Ann Oncol. 2017;28:3092-3097.
Jonna S, Feldman RA, Swensen J, et al. Detection of NRG1 gene fusions in solid tumors. Clin Cancer Res. 2019;25:4966-4972.
Schram AM, Drilon A, Macarulla Mercade T, et al. A phase 2 basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumors. Presented at: 2019 European Hematology Association Annual Meeting; June 13-16, 2019. Abstract 7145.
Schram AM, Drilon A, Macarulla Mercade T, et al. A phase II basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumours. Presented at: 2019 European Hematology Association Annual Meeting; June 13-16, 2019. Abstract 685TiP.
Liu SV. NRG1 fusions: biology to therapy. Lung Cancer. 2021;158:25-28.
Dimou A, Ross Camidge D. Detection of NRG1 fusions in solid tumors: rare gold? Clin Can Res. 2019;25:4865-4867.
Laskin J, Liu SV, Tolba K, et al. NRG1 fusion-driven tumors: biology, detection, and the therapeutic role of afatinib and other ErbB-targeting agents. Ann Oncol. 2020;31:1693-1703.
Jones MR, Williamson LM, Topham JT, et al. NRG1 gene fusions are recurrent, clinically actionable gene rearrangements in KRAS wild-type pancreatic ductal adenocarcinoma. Clin Cancer Res. 2019;25:4674-4681.
Heining C, Horak P, Uhrig S, et al. NRG1 fusions in KRAS wild-type pancreatic cancer. Cancer Discov. 2018;8:1087-1095.
Jonna S. Detection of NRG1 gene fusions in NSCLC. Presented at: 2020 International Association for the Study of Lung Cancer Targeted Therapies of Lung Cancer Meeting; February 19-22, 2020. Abstract OA3.
Drilon A, Duruisseaux M, Han J-Y, et al. Clinicopathologic features and response to therapy of NRG1 fusion-driven lung cancers: the eNRGy1 global multicenter registry. J Clin Oncol. 2021;39:2791-2802.
Muscarella LA, Trombetta D, Pio Fabrizio F, et al. ALK and NRG1 fusions coexist in a patient with signet ring cell lung adenocarcinoma. J Thorac Oncol. 2017;12:e161-e163.
Trombetta D, Graziano P, Scarpa A, et al. Frequent NRG1 fusions in Caucasian pulmonary mucinous adenocarcinoma predicted by Phospho-ErbB3 expression. Oncotarget. 2018;9:9661-9671.
Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT): a hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17:251-264.
Zehir A, Benayed R, Shah RH, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23:703-713.
Davies KD, Aisner DL. Wake up and smell the fusions: single-modality molecular testing misses drivers. Clin Cancer Res. 2019;25:4586-4588.
Zheng Z, Liebers M, Zhelyazkova B, et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med. 2014;20:1479-1484.
Jonna S, Feldman R, Ou SHI, et al. Characterization of NRG1 gene fusion events in solid tumors. Presented at: 56th Annual Meeting of the American Society of Clinical Oncology; May 29-31, 2020. Abstract 3113.
Drilon A, Somwar R, Mangatt BP, et al. Response to ERBB3-directed targeted therapy in NRG1-rearranged cancers. Cancer Discov. 2018;8:686-695.
Benayed R, Offin M, Mullaney K, et al. High yield of RNA sequencing for targetable kinase fusions in lung adenocarcinomas with no mitogenic driver alteration detected by DNA sequencing and low tumor mutation burden. Clin Cancer Res. 2019;25:4712-4722.
Robert NJ, Nwokeji ED, Espirito JL, et al. Biomarker tissue journey among patients (pts) with untreated metastatic non-small cell lung cancer (mNSCLC) in the U.S. Oncology Network community practices. Presented at: 57th Annual Meeting of the American Society of Clinical Oncology; June 4-8, 2021. Abstract 9004.
Liu SV, Duruisseaux M, Tolba K, et al. Targeting NRG1-fusions in multiple tumour types: afatinib as a novel potential treatment option. Presented at: 2019 European Society for Medical Oncology Congress; September 27 - October 1, 2019. Abstract 4097.
Cadranel J, Liu SV, Duruisseaux M, et al. Therapeutic potential of afatinib in NRG1 fusion-driven solid tumors: a case series. Oncologist. 2021;26:7-16.
Schram AM, O’Reilly EM, O’Kane GM, et al. Efficacy and safety of zenocutuzumab in advanced pancreas cancer and other solid tumors harboring NRG1 fusions. Presented at: 2021 American Society of Clinical Oncology Virtual Annual Meeting; June 4-8, 2021. Abstract 3003.
Duruisseaux M, Laskin JJ, Tolba K, et al. Targeting NRG1-fusions in lung adenocarcinoma: afatinib as a novel potential treatment strategy. Presented at: 2019 International Association for the Study of Lung Cancer World Conference on Lung Cancer; September 7-10, 2019. Abstract P1.14-25.
Liu SV, Villarux LC, Lee VHF, et al. First analysis of RAIN-701: study of tarloxotinib in patients with non-small cell lung cancer (NSCLC) EGFR exon 20 insertion, HER2-activating mutations & other solid tumours with NRG1/ERBB gene fusions. Presented at: 2020 European Hematology Association Annual Meeting; September 19-21, 2020. Abstract LBA61.
Odintsov I, Lui AJW, Sisso WJ, et al. The anti-HER3 mAb seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic NRG1 Clin Cancer Res. 2021;27;3154-3166.
Denlinger CS, Keedy VL, Moyo V, et al. Phase I dose escalation study of seribantumab (MM-121), an anti-HER3 monoclonal antibody, in patients with advanced solid tumors. Invest New Drugs. 2021;39:1604-1612.

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