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Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care

3632 - Phase II open-label, global study evaluating dabrafenib in combination with trametinib in pediatric patients with BRAF V600–mutant high-grade glioma (HGG) or low-grade glioma (LGG)


22 Oct 2018


Poster display session: Breast cancer - early stage, locally advanced & metastatic, CNS tumours, Developmental therapeutics, Genitourinary tumours - prostate & non-prostate, Palliative care, Psycho-oncology, Public health policy, Sarcoma, Supportive care


Cytotoxic Therapy;  Targeted Therapy;  Cancer in Adolescents and Young Adults (AYA)

Tumour Site

Central Nervous System Malignancies


Darren Hargrave


Annals of Oncology (2018) 29 (suppl_8): viii122-viii132. 10.1093/annonc/mdy273


D. Hargrave1, O. Witt2, K. Cohen3, R. Packer4, A. Lissat5, U. Kordes6, T.W. Laetsch7, L. Hoffman8, A. Lassaletta9, N.U. Gerber10, S. Gilheeney11, S. Holm12, C. Kramm13, D. Sumerauer14, C. Reitmann15, M.W. Russo16, E. Bouffet17

Author affiliations

  • 1 Haematology And Oncology Department, Great Ormond Street Hospital for Children, WC1N 3JH - London/GB
  • 2 Kitz Clinical Trial Unit, Ccu Pediatric Oncology And Department Of Pediatric Oncology, Hopp Children’s Cancer Center at the NCT Heidelberg, Heidelberg/DE
  • 3 The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Hospital, Baltimore/US
  • 4 Center For Neuroscience And Behavioral Medicine, Children's National Health System, Washington/US
  • 5 Department Of Pediatrics, Charité – Universitätsmedizin Berlin, Berlin/DE
  • 6 Department Of Pediatric Hematology And Oncology, University Medical Center Eppendorf, Hamburg/DE
  • 7 Department Of Pediatrics, The University of Texas Southwestern Medical Center and Children’s Health, 75390-8576 - Dallas/US
  • 8 Pediatric Hematology / Oncology Department, Children’s Hospital Colorado, Aurora/US
  • 9 Pediatric Hematology / Oncology Department, Hospital Infantil Universitario Niño Jesus, Madrid/ES
  • 10 Early Phase Clinical Trials Unit, Department Of Oncology, University Children’s Hospital, Zurich/CH
  • 11 Department Of Pediatric Neuro-oncology, Memorial Sloan Kettering Cancer Center, New York/US
  • 12 Division Of Pediatric Oncology, Karolinska Institutet, Stockholm/SE
  • 13 Division Of Pediatric Hematology And Oncology, University of Goettingen, Goettingen/DE
  • 14 Department Of Paediatric Haematology And Oncology, Faculty Hospital Motol, Prague/CZ
  • 15 Global Development Operations Trial Management, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 16 Global Drug Development, Novartis Pharmaceuticals Corporation, East Hanover/US
  • 17 Division Of Haematology/oncology, Hospital for Sick Children, University of Toronto, Toronto/CA


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Abstract 3632


Activation of the MAPK pathway via the BRAF V600 mutation has been observed in several tumors. This mutation is observed in a subset of pediatric brain tumors, including HGG and LGG for which limited therapeutic options are currently available. In a phase I/II clinical trial of pediatric patients (pts) with recurrent or refractory BRAF V600–mutant relapsed tumors, the BRAF inhibitor dabrafenib demonstrated its efficacy, including complete responses, in pediatric pts with HGG and LGG. As the combination of dabrafenib plus the MEK inhibitor trametinib has resulted in improved efficacy in multiple adult BRAF V600–mutant tumors, including melanoma and non-small cell lung cancer, this combination warrants further investigation in pediatric pts with gliomas bearing the same mutation.

Trial design

This global, open-label, phase II study (NCT02684058) will evaluate the anti-tumor activity of the combination of dabrafenib plus trametinib in 2 pediatric glioma cohorts recruiting from up to 70 sites across 17 countries. The single-arm BRAF V600–mutated HGG cohort of approximately 40 pts (aged ≥ 6 and < 18 y) with relapsed or refractory disease will be treated with dabrafenib twice daily (BID) plus trametinib once daily (QD) based on age and weight. The primary endpoint for this cohort is overall response rate (ORR) per investigator’s assessment according to Response Assessment in Neuro-Oncology (RANO) criteria. The BRAF V600–mutated LGG cohort of approximately 102 chemotherapy-naive pts (aged ≥ 6 and < 18 y) with unresectable disease will be randomized 2:1 to receive either dabrafenib (BID) plus trametinib (QD) or carboplatin plus vincristine. The primary endpoint for the LGG cohort is ORR per independent assessment according to RANO criteria. Pt crossover from the chemotherapy arm to the experimental arm will be allowed after independent confirmation of radiologic disease progression. Key secondary endpoints for both cohorts include duration of response, progression-free survival, time to response, clinical benefit rate, overall survival, and safety/tolerability.

Clinical trial identification


Legal entity responsible for the study

Novartis Pharmaceuticals Corporation.


Novartis Pharmaceuticals Corporation.

Editorial Acknowledgement

Medical writing assistance was provided by William Fazzone, PhD (ArticulateScience LLC), funded by Novartis Pharmaceuticals Corporation.


D. Hargrave: Consultancy: Novartis. O. Witt: Membership on board of directors or advisory committees: Novartis; Study committee on selumetinib trial: AzstraZeneca. K. Cohen: Research Funding: Novartis; Membership on board of directors or advisory committees: Novartis. T.W. Laetsch: Consultancy: Novartis, Loxo Oncology, Bayer; Research funding: Pfizer. A. Lassaletta: Consultancy: Shire, Clinigen. C. Kramm: Research funding: Novartis, Eisai, Boehringer Ingelheim, Merck. C. Reitmann, M.W. Russo: Employment: Novartis; E. Bouffet: Research funding to institution: Roche, Bristol-Myers Squibb.

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