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Proffered paper session - Developmental therapeutics

1971 - Larotrectinib efficacy and safety in TRK fusion cancer: an expanded clinical dataset showing consistency in an age and tumor agnostic approach


21 Oct 2018


Proffered paper session - Developmental therapeutics


Clinical Research;  Targeted Therapy

Tumour Site


Ulrik Lassen


Annals of Oncology (2018) 29 (suppl_8): viii133-viii148. 10.1093/annonc/mdy279


U.N. Lassen1, C.M. Albert2, S. Kummar3, C.M. van Tilburg4, S.G. Dubois5, B. Geoerger6, L. Mascarenhas7, N. Federman8, R.J. Schilder9, F. Doz10, J.D. Berlin11, D. Oh12, S.S. Bielack13, R. McDermott14, D.S.W.S. Tan15, S. Cruickshank16, N.C. Ku16, M.C. Cox16, A. Drilon17, D.S. Hong18

Author affiliations

  • 1 Finsen Center, Dept. Of Oncology, Phase 1 Unit, Copenhagen University Hospital - Rigshospitalet, 2100 - Copenhagen/DK
  • 2 Pediatric Oncology, Seattle Children’s Hospital, University of Washington, Fred Hutchinson Cancer Research Center, Seattle/US
  • 3 Medical Oncology, Stanford Cancer Institute, Stanford University, 94305 - Stanford/US
  • 4 Pediatric Oncology, Hopp Children’s Cancer Center at the NCT Heidelberg (KiTZ), Heidelberg University Hospital and German Cancer Research Center (DKFZ), Heidelberg/DE
  • 5 Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston/US
  • 6 Department Of Pediatric And Adolescent Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 7 Oncology, Children’s Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles/US
  • 8 Pediatric Oncology, University of California, Los Angeles, Los Angeles/US
  • 9 Medical Oncology, Thomas Jefferson University, Philadelphia/US
  • 10 Pediatric Oncology, Institut Curie and University Paris Descartes, Paris/FR
  • 11 Medicine, Vanderbilt Ingram Cancer Center, 37232-6307 - Nashville/US
  • 12 Medical Oncology, Seoul National University Hospital, 110-744 - Seoul/KR
  • 13 Pediatric Oncology, Klinikum Stuttgart - Olgahospital, 70174 - Stuttgart/DE
  • 14 Medical Oncology, AMNCH Adelaide and Meath Hospital, 24 - Dublin/IE
  • 15 Medical Oncology, National Cancer Center, 16910 - Singapore/SG
  • 16 Clinical Development, Loxo Oncology, 94080 - South San Francisco/US
  • 17 Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 18 Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 77035 - Houston/US


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Abstract 1971


TRK fusion cancer results from gene fusions involving NTRK1, NTRK2 or NTRK3. Larotrectinib, the first selective TRK inhibitor, has demonstrated an overall response rate (ORR) of 75% with a favorable safety profile in the first 55 consecutively enrolled adult and pediatric patients with TRK fusion cancer (Drilon et al.,NEJM2018). Here, we report the clinical activity of larotrectinib in an additional 35 TRK fusion cancer patients and provide updated follow-up of the primary analysis set (PAS) of 55 patients as of 19thFeb 2018.


Patients with TRK fusion cancer detected by molecular profiling from 3 larotrectinib clinical trials (NCT02122913, NCT02637687, and NCT02576431) were eligible.Larotrectinib was administered until disease progression, withdrawal, or unacceptable toxicity. Disease status was assessed using RECIST version 1.1.


As of Feb 2018, by independent review, 6 PRs in the PAS deepened to CRs. The median duration of response (DoR) and progression-free survival in the PAS had still not been reached, with 12.9 months median follow-up. At 1 year, 69% of responses were ongoing, 58% of patients remained progression-free and 90% of patients were alive. An additional 19 children and 25 adults (age range, 0.1-78 years) with TRK fusion cancer were enrolled after the PAS, and included cancers of the salivary gland, thyroid, lung, colon, melanoma, sarcoma, GIST and congenital mesoblastic nephroma. In 35 evaluable patients, the ORR by investigator assessment was 74% (5 CR, 21 PR, 6 SD, 2 PD, 1 not determined). In these patients, with median follow-up of 5.5 months, median DoR had not yet been reached, and 88% of responses were ongoing at 6 months, consistent with the PAS. Adverse events (AEs) were predominantly grade 1, with dizziness, increased AST/ALT, fatigue, nausea and constipation the most common AEs reported in ≥ 10% of patients. No AE of grade 3 or 4 related to larotrectinib occurred in more than 5% of patients.


TRK fusions are detected in a broad range of tumor types. Larotrectinib is an effective age- and tumor-agnostic treatment for TRK fusion cancer with a positive safety profile. Screening patients for NTRK gene fusions in solid- and brain tumors should be actively considered.

Clinical trial identification

NCT02122913, NCT02637687, and NCT02576431.

Legal entity responsible for the study

Loxo Oncology, Inc.


Loxo Oncology, Inc.

Editorial Acknowledgement


S.G. Dubois: Fees for consulting and advisory board roles: Loxo Oncology. N. Federman: Honoraria from ad boards: Bayer AG and Loxo Oncology. S. Cruickshank: Paid consultant: Loxo Oncology, Inc. N.C. Ku, M.C. Cox: Employee and stockholder: Loxo Oncology, Inc. All other authors have declared no conflicts of interest.

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