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Poster Display session 2

7145 - A phase 2 basket study of MCLA-128, a bispecific antibody targeting the HER3 pathway, in NRG1 fusion-positive advanced solid tumors


29 Sep 2019


Poster Display session 2


Alison Schram


Annals of Oncology (2019) 30 (suppl_5): v253-v324. 10.1093/annonc/mdz247


A.M. Schram1, A. Drilon2, T. Macarulla Mercade3, E.M. O'Reilly4, J.A. Rodon5, B.M. Wolpin6, S.I. Ou7, D. Kim8, J.C. Yang9, Y.C.J. Lam10, A. Varga11, A.J. de Langen12, P.O. Witteveen13, V. Boni14, G. Cerea15, M. Duruisseaux16, S.V. Liu17, E. Wasserman18, D.M. Hyman19, J. Tabernero20

Author affiliations

  • 1 Department Of Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2 Clinical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 3 Medical Oncology, Vall d'Hebron University Hospital and Vall d'Hebron Institute of Oncology, 08035 - Barcelona/ES
  • 4 Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 5 Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 6 Division Of Gastrointestinal Oncology, Dana-Farber Cancer Institute, Boston/US
  • 7 Medicine, Chao Family Comprehensive Cancer Center, University of California Irvine Healthcare, 92697 - Orange/US
  • 8 Hemato Oncology, Medical Oncology Center, Personalized Cancer Medicine Center Hemato-oncology, Seoul National University Hospital, 03080 - Seoul/KR
  • 9 Department Of Oncology, National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei/TW
  • 10 Division Of Medical Oncology, National Cancer Centre Singapore, 169610 - Singapore/SG
  • 11 Medical Oncology, Gustave Roussy, Villejuif/FR
  • 12 Medical Oncology, Netherlands Cancer Institute (NKI), Amsterdam/NL
  • 13 Medical Oncology, UMC Utrecht Cancer Center, Utrecht/NL
  • 14 Oncology, START Madrid-CIOCC, 28050 - Madrid/ES
  • 15 Department Of Hematology And Oncology, Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda and Università degli Studi di Milano, Milan/IT
  • 16 Department Of Pneumonology, Hôpital Louis Pradel-Hospices Civils de Lyon, 69500 - Bron/FR
  • 17 Medical Oncology, Lombardi Cancer Center Georgetown University, 20007 - Washington/US
  • 18 Clinical Oncology, Merus, Utrecht/NL
  • 19 Department Of Medicine, Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College, 10065 - New York/US
  • 20 Medical Oncology, Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology (VHIO), 08001 - Barcelona/ES


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Abstract 7145


NRG1 fusions are oncogenic drivers across various cancers. NRG1 fusion proteins bind to HER3, leading to HER2/HER3 heterodimerization, increased downstream signaling, and tumor growth. Clinical responses to anti-HER3 antibodies or HER2 tyrosine kinase inhibitors have been reported. In contrast to these agents, MCLA-128 is a HER2/HER3 bispecific antibody that blocks both NRG1 binding and HER2/3 dimerization. MCLA-128 has demonstrated potent in vitro and in vivo activity in NRG1-fusion positive models. These data support the evaluation of MCLA-128 in patients with NRG1 fusion-positive tumors using a basket approach.

Trial design

This is a global, open-label, multicenter phase 2 basket trial of MCLA-128 in patients with solid tumors harboring NRG1 gene fusions. Main eligibility criteria are locally advanced unresectable or metastatic cancers harboring an NRG1 fusion, and failure under prior standard therapy appropriate for the tumor type and disease stage. Genomic screening of tumor tissue is done at a local laboratory (with post-hoc central confirmation) or central laboratory (RNA sequencing). Three NRG1 fusion-positive tumor cohorts are being evaluated: pancreatic cancer, NSCLC, and other solid tumors. The sample size for the first two cohorts is up to 25 patients; the basket group may enroll up to 40 patients. The primary endpoint for all cohorts is investigator-assessed objective response rate (RECIST v1.1). The key secondary endpoint is duration of response. Other secondary endpoints include progression-free and overall survival. Eligible patients receive a bi-weekly dosing regimen of 750 mg of MCLA-128 (2-hour infusion), every 2 weeks, in 4-week cycles. The study is actively accruing patients in North America, Europe, and Asia.

Clinical trial identification


Editorial acknowledgement

Sarah Mackenzie (PhD) from Oncology Therapeutics Development.

Legal entity responsible for the study

Merus N.V.


Merus N.V.


A. Drilon: Honoraria (self), Advisory / Consultancy: Ignyta/Genentech/Roche, Loxo/Bayer/Lilly, Takeda/Ariad/Millenium, TP Therapeutics, AstraZeneca, Pfizer, Blueprint, Helsinn, Beigene, BergenBio, Hengrui, Exelixis, Tyra, Verastem, MORE Health; Research grant / Funding (institution): GlaxoSmithKline, Teva, Taiho, PharmaMar; Research grant / Funding (self): Foundation Medicine; Non-remunerated activity/ies: Wolters Kluwer, Merck, Puma . T. Macarulla Mercade: Honoraria (self): Shire Pharmaceuticals, Roche, Tesaro, Batxer, Sanofi, Celgene, QED Therapeutics, Genzyme Europe, Baxalta, Bayer, Incyte, Servier, Lilly, Ipsen; Travel / Accommodation / Expenses: Merck, H3 Biomedicine, Bayer, Sanofi, Servier. E.M. O’Reilly: Research grant / Funding (institution): Genentech, BMS, Halozyme, Celgene, MabVax Therapeutics, ActaBiologica, AstraZeneca, Silenseed, Pfizer, Polaris; Advisory / Consultancy: CytomX Therapeutics, BioLineRx, Targovax, Ipsen, Celgene, Bayer, Polaris, Sobi, Merck. J.A. Rodon: Travel / Accommodation / Expenses: European Journal of Cancer, Vall d’Hebron Institut of Oncology, Chinese University of Hong Kong, SOLTI, Elsevier, GlaxoSmithKline, ESMO, US Department of Defense, Louissiana State University, Hunstman Cancer Institute, Cancer Core Europe, Karolinska Cancer; Advisory / Consultancy: Novartis, Eli Lilly, Orion Pharmaceuticals, Servier Pharmaceuticals, Peptomyc, Merck Sharp & Dohme, Kelun Pharmaceutical/Klus Pharma, Spectrum Pharmaceuticals Inc, Pfizer, Roche Pharmaceuticals, Ellipses Pharma; Research grant / Funding (institution): Bayer and Novartis; Non-remunerated activity/ies: Spectrum Pharmaceuticals, Tocagen, Symphogen, BioAtla, Pfizer, GenMab, CytomX, Kelun-Biotech, Takeda-Millenium, GlaxoSmithKline, Ipsen. B.M. Wolpin: Research grant / Funding (institution): Celgene Inc., Eli Lilly and Company; Advisory / Consultancy: BioLineRx Ltd., Celgene Inc., G1 Therapeutics Inc., and GRAIL Inc. S.I. Ou: Honoraria (self): Pfizer, Roche/Genentech/Ignyta/Foundation Medicine, Astra Zeneca, Merck, Takeda/ARIAD; Advisory / Consultancy: Turning Point (TP) Therapeutics; Shareholder / Stockholder / Stock options: Turning Point Therapeutics. J.C. Yang: Honoraria (self): Boehringer Ingelheim, Eli Lilly, Bayer, Roche/, Chugai, Astellas, Merck Serono, MSD, Pfizer, Novartis, Celgene, Merrimack, Yuhan Pharmaceuticals, BMS, Ono Pharmaceuticals, Daiichi Sankyo, Hansoh Pharmaceuticals, Takeda Pharmaceuticals, Blueprint Medicines. A. Varga: Research grant / Funding (institution): Astrazeneca, BMS, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi; Research grant / Funding (institution), drug supply: Astrazeneca, Bayer, BMS, Boringher Ingelheim, Johnson & Johnson, Lilly, Medimmune, Merck, NH TherAGuiX, Pfizer, Roche. A.J. de Langen: Research grant / Funding (institution): Boehringer, AstraZeneca, Merck / MSD, BMS; Non-remunerated activity/ies, non-financial support: Roche; Honoraria (self): Merck / MSD, BMS. V. Boni: Honoraria (self), Research grant / Funding (institution): Loxo Therapeutics; Advisory / Consultancy: OncoArt; Advisory / Consultancy: Guidepoint; Speaker Bureau / Expert testimony: SOLTI; Research grant / Funding (institution): Sanofi; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Kura; Research grant / Funding (institution): Cytomex; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Seattle Genetics; Travel / Accommodation / Expenses: START. M. Duruisseaux: Advisory / Consultancy, Research grant / Funding (institution), Personal fees for expertise / Consulting : Pfizer; Advisory / Consultancy, Research grant / Funding (institution), Personal fees for expertise / Consulting : Novartis; Research grant / Funding (institution): Nanostring; Advisory / Consultancy, Personal fees for expertise / Consulting : Roche; Advisory / Consultancy, Personal fees for expertise / Consulting : Takeda; Advisory / Consultancy, Personal fees for expertise / Consulting: AbbVie; Advisory / Consultancy, Personal fees for expertise / Consulting: MSD; Advisory / Consultancy, Personal fees for expertise / Consulting : BI; Advisory / Consultancy, Personal fees for expertise / Consulting : BMS; Advisory / Consultancy, Personal fees for expertise / Consulting : AZ. S.V. Liu: Advisory / Consultancy: Apollomics, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, G1 Therapeutics, Genentech/Roche, Heron, Ignyta, Inivata, Janssen, Lilly, Merck, Pfizer, Regeneron, Taiho (DSMB), Takeda/Ariad, Tempus; Research grant / Funding (institution): Alkermes, AstraZeneca, Bayer, Blueprint, Bristol-Myers Squibb, Clovis, Corvus, Debiopharm, Esanex, Genentech/Roche, Ignyta, Lilly, Lycera, Merck, Molecular Partners, OncoMed, Pfizer, Rain Therapeutics. E. Wasserman: Full / Part-time employment: Merus NV; Shareholder / Stockholder / Stock options: Merus NV. D.M. Hyman: Shareholder / Stockholder / Stock options: Fount; Consulting or Advisory Role: Chugai Pharma, Boehringer Ingelheim, AstraZeneca, Pfizer, Bayer, Genentech, Fount; Research grant / Funding (institution): AstraZeneca, Puma Biotechnology, Loxo, Bayer; Travel, Accommodations, Expenses: Genentech, Chugai Pharma. J. Tabernero: Advisory / Consultancy: Array Biopharma, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Chugai, Genentech, Inc., Genmab A/S, Halozyme, Imugene Limited, Inflection Biosciences Limited, Ipsen, Kura Oncology, Lilly, MSD, Menarini, Merck Serono, Merrimack, Merus, Molecular Part. All other authors have declared no conflicts of interest.

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