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Poster Display session 3

4559 - Treatment with BLU-667, a potent and selective RET inhibitor, provides rapid clearance of ctDNA in Patients with RET-altered Non-Small Cell Lung Cancer (NSCLC) and Thyroid Cancer


30 Sep 2019


Poster Display session 3


Translational Research

Tumour Site

Thyroid Cancer;  Non-Small Cell Lung Cancer


Giuseppe Curigliano


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


G. Curigliano1, V. Subbiah2, J.F. Gainor3, D.H. Lee4, M.H. Taylor5, V. Zhu6, R.C. Doebele7, G. Lopes8, C. Baik9, E. Garralda10, S.M. Gadgeel11, D. Kim12, C.D. Turner13, M. Palmer14, S. Miller14

Author affiliations

  • 1 Division Of Early Drug Development, European Institute of Oncology, 20146 - Milan/IT
  • 2 Department Of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3 Department Of Medicine, Massachusetts General Hospital, 02114 - Boston/US
  • 4 Department Of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 05505 - Seoul/KR
  • 5 Knight Cancer Institute, The Knight Cancer Institute, Oregon Health & Science University, 97239 - Portland/US
  • 6 Department Of Medicine, Division Of Hematology/oncology, University of California, Irvine School of Medicine, 92868 - Orange/US
  • 7 Division Of Medical Oncology, University of Colorado, 80045 - Aurora/US
  • 8 Sylvester Comprehensive Cancer Center, Sylvester Comprehensive Cancer Center, University of Miami Health System, 33136 - Miami/US
  • 9 Seattle Cancer Care Alliance Inpatient Unit, University of Washington/Seattle Cancer Care Alliance, 98109 - Seattle/US
  • 10 Vall D’hebron Institute Of Oncology, Vall d’Hebron Institute of Oncology, Vall d’Hebron University Hospital, 08035 - Barcelona/ES
  • 11 Department Of Internal Medicine, University of Michigan, 48201 - Ann Arbor/US
  • 12 Hemato Oncology, Medical Oncology Center, Personalized Cancer Medicine Center Hemato-oncology, Seoul National University Hospital, 03080 - Seoul/KR
  • 13 Clinical Development, Blueprint Medicines Corporation, 2139 - Cambridge/US
  • 14 Translational Medicine, Blueprint Medicines Corporation, 2139 - Cambridge/US


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Abstract 4559


BLU667, an investigational agent, is a potent and selective inhibitor of oncogenic rearranged during transfection (RET) alterations and predicted resistance mutations. Up to 90% of advanced medullary thyroid cancer (MTC) is characterized by single nucleotide variants and short insertions/deletions in the RET gene. In NSCLC, 1-2% of patients (pts) harbor rearrangements resulting in RET fusions. In the first-in-human ARROW study (NCT03037385), BLU-667 has demonstrated significant clinical activity in RET-altered NSCLC and MTC and has been well tolerated. Previous data has shown that early declines in circulating tumor DNA (ctDNA) may predict for treatment outcome. We investigated the change in ctDNA levels from baseline following treatment with BLU-667 and whether early changes in ctDNA during treatment were associated with clinical responses and outcomes.


Blood was collected at baseline and prespecified time points during treatment. Plasma from 111 pts with locally documented RET-altered MTC and NSCLC were profiled with the Personal Genome Diagnostics PlasmaSELECT™ R64 sequencing panel.


RET fusions were detected at baseline in 45/63 (71%) pts with NSCLC and RET mutations in 35/48 (73%) pts with MTC. Baseline ctDNA mutant allele fraction (MAF; MTC) or unique fusion reads (NSCLC) correlated with the sum of target lesions (p<0.01). BLU-667 led to rapid RET ctDNA declines in almost all pts and across all doses (60-600 mg QD, 100-200 mg BID). Eighty-one percent of pts with NSCLC and detectable ctDNA at baseline had undetectable RET ctDNA after 8 weeks of treatment. Clearance of RET fusions in NSCLC was observed for multiple fusion partners including CCDC6 and KIF5B. Forty-one percent of pts with MTC harboring somatic RET mutations also had undetectable RET ctDNA after 8 weeks. The correlation between changes in ctDNA levels and clinical outcomes are currently not mature and will be reported at the meeting.


Treatment with BLU-667 led to a robust and rapid decline in ctDNA in almost all patients regardless of treatment dose or tumor diagnosis and in NSCLC irrespective of fusion partner studied.

Clinical trial identification


Editorial acknowledgement

Legal entity responsible for the study

Blueprint Medicines Corporation.


Blueprint Medicines Corporation.


G. Curigliano: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Seattle Genetics; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pfizer. V. Subbiah: Advisory / Consultancy: MedImmune; Research grant / Funding (institution): Novartis (Inst), GlaxoSmithKline (Inst), NanoCarrier (Inst), Northwest Biotherapeutics (Inst), Genentech (Inst), Roche (Inst), Berg Pharma (Inst), Bayer AG (Inst), Incyte (Inst), Fujifilm (Inst), PharmaMar (Inst), D3 Oncology Solutions (Inst), Pfizer (Ins; Travel / Accommodation / Expenses: PharmaMar, Bayer AG. J.F. Gainor: Honoraria (self): Merck, Incyte, ARIAD Pharmaceuticals, Novartis, Pfizer; Advisory / Consultancy: Genentech, Bristol-Myers Squibb, Theravance, Loxo, Takeda, Array BioPharma, Amgen, Merck, Agios, Regeneron, Oncorus, Jounce Therapeutics; Research grant / Funding (institution): Merck (Inst), Novartis (Inst), Genentech (Inst), Bristol-Myers Squibb (Inst), Adaptimmune (Inst), AstraZeneca (Inst), ARIAD Pharmaceuticals (Inst), Jounce Therapeutics (Inst), Blueprint Medicines (Inst), Moderna Therapeutics (Inst), Tesaro (Inst), Alexo T. D.H. Lee: Honoraria (self): AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, CJ Healthcare, Eli Lilly, Janssen, Merck, MSD, Mundipharma, Novartis, Ono, Pfizer, Roche, Samyang Biopharm and ST Cube; Advisory / Consultancy: Ministry of Food and Drug Safety, Korea, Health Insurance Review and Assessment Service, Korea, National Evidence-based Collaborating Agency, Korea, and National Cancer Control Planning Board, Korea. M.H. Taylor: Honoraria (self), Advisory / Consultancy: BMS, Eisai Inc, Array Biopharma, Bayer, LOXO, Blueprint, Arqule, Novartis; Speaker Bureau / Expert testimony: BMS, Eisai Inc; Research grant / Funding (institution): BioAtla; Travel / Accommodation / Expenses: BMS, Eisai Inc, Array Biopharma, Bayer, Loxo, Blueprint. V. Zhu: Honoraria (self), Speaker Bureau / Expert testimony: AstraZeneca, Roche-Foundation Medicine, Roche/Genentech, Takeda; Advisory / Consultancy, Shareholder / Stockholder / Stock options: TP Therapeutics. R.C. Doebele: Honoraria (self): Pfizer, AstraZeneca, ARIAD Pharmaceuticals, Guardant Health, Takeda Pharmaceuticals, Spectrum Pharmaceuticals, Trovagene; Advisory / Consultancy: Pfizer, OncoMed Pharmaceuticals, Trovagene, Ignyta, GreenPeptide, AstraZeneca; Research grant / Funding (institution): Ignyta (Inst); Travel / Accommodation / Expenses: Ignyta, ARIAD Pharmaceuticals, Guardant Health; Shareholder / Stockholder / Stock options: Rain Therapeutics; Licensing / Royalties: Other Intellectual Property: Licensing fees from Abbott Molecular for patent PCT/US2013/057495, licensing fees from Ignyta for biologic materials (Inst). G. Lopes: Advisory / Consultancy: Pfizer; Research grant / Funding (self): AstraZeneca; Research grant / Funding (institution): Merck Sharp & Dohme (Inst); EMD Serono (Inst), AstraZeneca (Inst), AstraZeneca, Blueprint Medicines (Inst), Tesaro (Inst), Bavarian Nordic (Inst), Novartis (Inst), G1 Therapeutics (Inst). E. Garralda: Research grant / Funding (self), Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: BMS, Menarini, Glycotope; Licensing / Royalties: MSD. S.M. Gadgeel: Advisory / Consultancy: Pfizer, Genentech, ARIAD Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, AbbVie; Speaker Bureau / Expert testimony: AstraZeneca; Research grant / Funding (self), Research grant / Funding (institution): Merck; Research grant / Funding (institution): Pfizer (Inst), Merck, Genentech (Inst), Blueprint Medicines (Inst), ARIAD Pharmaceuticals (Inst), Takeda (Inst); Travel / Accommodation / Expenses: ARIAD Pharmaceuticals, Takeda. C.D. Turner: Full / Part-time employment: Blueprint Medicines Corporation. M. Palmer: Full / Part-time employment: Blueprint Medicines Corporation. S. Miller: Full / Part-time employment: Blueprint Medicines Corporation. All other authors have declared no conflicts of interest.

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