Abstract 7145
Background
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
NCT02912949.
Editorial acknowledgement
Sarah Mackenzie (PhD) from Oncology Therapeutics Development.
Legal entity responsible for the study
Merus N.V.
Funding
Merus N.V.
Disclosure
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.
Resources from the same session
5773 - A prospective study of diffusion-weighted magnetic resonance imaging for predicting outcome following chemoradiotherapy, in squamous cell carcinomas of the anus.
Presenter: Rebecca Muirhead
Session: Poster Display session 2
Resources:
Abstract
4581 - Timing to achieve complete response (CR) after definitive chemoradiotherapy (ChRT) in patients with squamous cell carcinoma of the anal (SCCAC) with and without HIV infection: a multicenter retrospective study
Presenter: Marcos Camandaroba
Session: Poster Display session 2
Resources:
Abstract
1712 - Planned organ preservation for T2 T3 M0 rectal adenocarcinoma. A possible option using chemoradiotherapy (CRT) and Contact X-ray Brachytherapy (CXB). A French multicenter study.
Presenter: Jean-Pierre Gérard
Session: Poster Display session 2
Resources:
Abstract
4639 - A Phase 1b Study of E7046 (AN0025) in Combination With Radiotherapy/Chemoradiotherapy (RT/CRT) in Preoperative Treatment of Rectal Cancer
Presenter: Lucjan Wyrwicz
Session: Poster Display session 2
Resources:
Abstract
2310 - Upfront radical surgery with total mesorectal excision (TME) versus preoperative chemoradiotherapy followed by TME in clinical stage II/III patients with rectal cancer: a propensity score analysis
Presenter: Ahrong Ham
Session: Poster Display session 2
Resources:
Abstract
2747 - Neoadjuvant chemoradiotherapy with/without lateral lymph node dissection for low rectal cancer: Which patients can benefit?
Presenter: Daisuke Nishizaki
Session: Poster Display session 2
Resources:
Abstract
2877 - The impact of completeness of chemotherapy on the efficacy of irinotecan in the preoperative chemoradiotherapy of locally advanced rectal cancer.
Presenter: Jingwen Wang
Session: Poster Display session 2
Resources:
Abstract
3050 - Feasibility of robot-assisted surgery in elderly patients with rectal cancer
Presenter: Wei-Chih Su
Session: Poster Display session 2
Resources:
Abstract
4109 - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: a case-control non-inferiority trial
Presenter: Valerii Ivanov
Session: Poster Display session 2
Resources:
Abstract
4813 - Differential of the nutritional index before and after neoadjuvant chemoradiotherapy as a prognostic factor of recurrence in patients with locally advanced adenocarcinoma of the rectum
Presenter: Leslie Navia-Ortuño
Session: Poster Display session 2
Resources:
Abstract