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Poster Display session 3

4097 - Targeting NRG1-fusions in multiple tumour types: Afatinib as a novel potential treatment option

Date

30 Sep 2019

Session

Poster Display session 3

Topics

Translational Research

Tumour Site

Presenters

Stephen V Liu

Citation

Annals of Oncology (2019) 30 (suppl_5): v760-v796. 10.1093/annonc/mdz268

Authors

S.V. Liu1, M. Duruisseaux2, K. Tolba3, E. Branden4, Y. Goto5, B.A. Weinberg6, D.J. Renouf7, R.C. Doebele8, C. Heining9, R.F. Schlenk10, P.K. Cheema11, J. Cadranel12, M.R. Jones13, A.E. Drilon14, D. Trombetta15, L.A. Muscarella15, A. Cseh16, F. Solca17, J.J. Laskin7

Author affiliations

  • 1 Division Of Medical Oncology, Georgetown University, 20007 - Washington/US
  • 2 Department Of Respiratory Medicine, Hospices Civils de Lyon Cancer Institute, Université Claude Bernard Lyon 1; UMR INSERM 1052 CNRS 5286 CRCL, Lyon/FR
  • 3 Knight Cancer Institute, Oregon Health and Science University, Portland/US
  • 4 Department Of Respiratory Medicine, Gävle Hospital, Gävle/SE
  • 5 Department Of Thoracic Oncology, National Cancer Center Hospital, Tokyo/JP
  • 6 Division Of Hematology And Oncology, Georgetown University Medical Center, Washington/US
  • 7 Division Of Medical Oncology, Department Of Medicine, University of British Columbia, BC Cancer, Vancouver/CA
  • 8 Department Of Medicine, University of Colorado Cancer Center, Aurora/US
  • 9 Department Of Translational Medical Oncology, National Center for Tumor Diseases Dresden, Dresden/DE
  • 10 Nct Trial Center, National Center Of Tumor Diseases Heidelberg, University Hospital and German Cancer Research Center, Heidelberg/DE
  • 11 Faculty Of Medicine, William Osler Health System, University of Toronto, Toronto/CA
  • 12 Department Of Pneumology, Assistance Publique Hôpitaux de Paris, Hôpital Tenon and Sorbonne Université, 75020 - Paris/FR
  • 13 Precision Oncology, Bioinformatic Business Area, QIAGEN Inc., Redwood City/US
  • 14 Department Of Medicine, Memorial Sloan Kettering Cancer Center, New York/US
  • 15 Laboratory Of Oncology, Fondazione IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Foggia/IT
  • 16 Department Of Medical Affairs, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna/AT
  • 17 Department Of Pharmacology, Boehringer Ingelheim RCV GmbH & Co. KG, Vienna/AT

Resources

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Abstract 4097

Background

Neuregulin 1 (NRG1) is a growth factor that binds HER3/4 and activates ErbB signalling pathways. NRG1 fusions function as oncogenic drivers and represent a potential therapeutic target across tumour types. Afatinib, an ErbB-family blocker, may be a treatment option for some patients (pts) with NRG1 fusion-positive (NRG1+) tumours, as supported by preclinical evidence and published case reports (Table).Table: 1969P

PatientTumour typeNRG1 fusion partnerBest responseDuration of response (months)Reference
iNon-mucinous lung ADCSLC3A2PR12Gay, et al. J Thoracic Oncol 2017
iiNon-mucinous lung ADCSDC4PR12Jones, et al. Ann Oncol 2017
iiiIMACD74PR10Gay, et al. J Thoracic Oncol 2017
ivIMACD74PR6.5Cheema, et al. J Thoracic Oncol 2017
vIMACD74SD3Drilon, et al. Cancer Discov 2018
viIMASDC4PD-Drilon, et al. Cancer Discov 2018
viiIMACD74PD-Drilon, et al. Cancer Discov 2018
viiiCholangiocarcinomaATP1B1PR8Jones, et al. Ann Oncol 2017
ixPancreatic ADCATP1B1PR3Heining, et al. Cancer Discov 2018
xOvarian cancerCLUSD-Murumagi. AACR 2019, abs 2945

ADC, adenocarcinoma; IMA, invasive mucinous lung adenocarcinoma; PD, progressive disease; PR, partial response; SD, stable disease

Methods

We report clinico-pathological and molecular characteristics of seven previously unreported cases of afatinib-treated NRG1+ tumours.

Results

Pt 1, 70 yo female, never-smoker with pan-wildtype, non-mucinous lung adenocarcinoma (ADC) received 15th-line afatinib for 24 mos (PR). An NRG1 fusion was subsequently identified. The pt was re-challenged with afatinib (PR, 3 mos) before switching to atezolizumab (PD). Pt 2, 66 yo female, never-smoker with metastatic (m) non-mucinous lung ADC. CD74-NRG1 fusion was identified, and 5th-line afatinib initiated. PR is ongoing after 14 mos. Pt 3, 68 yo male, >20 pack-yr smoking history with non-mucinous lung ADC. SDC4-NRG1 fusion was identified and 2nd-line afatinib initiated. Best response: SD, 4 mos. Pt 4, 43 yo female, non-smoker with advanced invasive mucinous lung ADC. CD74-NRG1 fusion was identified and 3rd-line afatinib initiated; PR is ongoing. Pt 5, 69 yo male, with KRAS-mutated m-colorectal cancer. Following a right hemicolectomy and liver/lung metastasectomies, a novel POMK-NRG1 fusion was detected and afatinib initiated (SD, 4 mos; treatment ongoing). Pts 6 and 7, male (54 & 59 yo) with KRAS WT, m-pancreatic cancers. Following PD on chemotherapy, APP-NRG1 and ATP1B1-NRG1 fusions, respectively, were detected and afatinib initiated. Pt 6 had a PR for 5 mos; treatment ongoing. Pt 7 had a PR for 5.5 mos.

Conclusions

These findings add to a growing body of evidence suggesting that afatinib is a potential treatment option for pts with NRG1+ tumours. Prospective study is ongoing in the Drug Rediscovery Protocol trial (DRUP; NCT02925234).

Clinical trial identification

N/A

Editorial acknowledgement

Medical writing assistance, supported financially by Boehringer Ingelheim, was provided by Christina Jennings, of GeoMed, an Ashfield company, part of UDG Healthcare plc.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

S.V. Liu: Advisory / Consultancy: Apollomics; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Celgene; Advisory / Consultancy: G1 Therapeutics; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy: Heron; Advisory / Consultancy: Ignyta; Advisory / Consultancy: Janssen; Advisory / Consultancy: Lilly; Advisory / Consultancy: Regeneron; Advisory / Consultancy: Takeda/Ariad; Advisory / Consultancy: Tempus; Advisory / Consultancy: Merck; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Taiho. M. Duruisseaux: Honoraria (self): Roche; Honoraria (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Merck Sharp and Dohme; Honoraria (self): AbbVie; Honoraria (self): Boerhinger Ingelheim. K. Tolba: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy: Boerhinger Ingelheim; Honoraria (self): Merck; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Foundation One. Y. Goto: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: Chugai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Taiho Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boerhinger Ingelheim; Speaker Bureau / Expert testimony, Research grant / Funding (self): Ono Pharmaceuticals; Speaker Bureau / Expert testimony, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Speaker Bureau / Expert testimony: Merck Sharp and Dohme; Speaker Bureau / Expert testimony: Shionogi Pharmaceuticals; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Novartis; Advisory / Consultancy: GSK; Research grant / Funding (self): AbbVie; Research grant / Funding (self): Dai-ichi Sankyo; Advisory / Consultancy: Kyorin. B.A. Weinberg: Travel / Accommodation / Expenses: Boehringer Ingelheim. D.J. Renouf: Honoraria (self): Celgene; Honoraria (self): Servier; Honoraria (self): Taiho; Honoraria (self): Ipsen; Honoraria (self): Bayer. R.C. Doebele: Advisory / Consultancy, Shareholder / Stockholder / Stock options, Licensing / Royalties: Rain Therapeutics; Honoraria (self): Guardant; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Trovagene; Advisory / Consultancy, Licensing / Royalties: Ariad; Advisory / Consultancy: Takeda; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Genentech/Roche; Advisory / Consultancy, Research grant / Funding (self), Licensing / Royalties: Ignyta; Advisory / Consultancy, Research grant / Funding (self), Licensing / Royalties: Loxo; Research grant / Funding (self): Mirati; Licensing / Royalties: Abbott Molecular; Licensing / Royalties: GVKbio; Licensing / Royalties: Chugai; Licensing / Royalties: Genentech; Licensing / Royalties: Foundation Medicine; Licensing / Royalties: Black Diamond. R.F. Schlenk: Research grant / Funding (self): Boehringer Ingelheim. P.K. Cheema: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Genomic Health; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Merck. J. Cadranel: Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Boehringer Ingelheim; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Lilly; Advisory / Consultancy: Merck Sharp and Dohme; Advisory / Consultancy, Research grant / Funding (self): Novartis; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda. M.R. Jones: Full / Part-time employment: Qiagen Inc. A.E. Drilon: Honoraria (self): Medscape; Honoraria (self): OncLive; Honoraria (self): PeerVoice; Honoraria (self): Physicians Education Resources; Honoraria (self): Tyra Biosciences; Honoraria (self): Targeted Oncology; Honoraria (self): MORE Health; Honoraria (self): Research to Practice; Honoraria (self): Foundation Medicine; Honoraria (self): Peerview; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy: Bayer; Advisory / Consultancy: Ignyta; Honoraria (self): Loxo; Advisory / Consultancy: TP Therapeutics; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Blueprint Medicines; Advisory / Consultancy: Takeda; Advisory / Consultancy: Helsinn Therapeutics; Advisory / Consultancy: BeiGene; Advisory / Consultancy: Hengrui Therapeutics; Advisory / Consultancy: Exelixis; Travel / Accommodation / Expenses, Other: Wolters Kluwer. L.A. Muscarella: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): Boehringer Ingelheim. A. Cseh: Full / Part-time employment: Boehringer Ingelheim; Shareholder / Stockholder / Stock options, Husband: Mylan. F. Solca: Full / Part-time employment: Boehringer Ingelheim RCV GmbH & Co KG. J.J. Laskin: Honoraria (self), Research grant / Funding (self): Roche Canada; Honoraria (self): Boehringer Ingelheim Canada; Honoraria (self): AstraZeneca Canada; Research grant / Funding (self): Pfizer Canada. All other authors have declared no conflicts of interest.

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