Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

NUTMEG: A randomised Phase II study of Nivolumab and Temozolomide (TMZ) vs TMZ alone in elderly patients with newly diagnosed Glioblastoma (GBM): Trial in progress   (#415)

Mustafa Khasraw 1 2 , Kerrie L McDonald 3 , Sonia Yip 4 , Roel Verhaak 5 , Amy Heimberger 6 , Merryn Hall 1 , Lauren Fisher 1 , Elizabeth Barnes 1 , Mark Rosenthal 7 , Craig Gedye 8 , Elizabeth Hovey 9 , Benjamin M Ellingson 10 , John Simes 1 , Annette Tongela 11 , Helen Wheeler 2 , Eng-Siew Koh 12 , Hui Gan 13 , Michael Back 2 , Zarnie Lwin 14 15
  1. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, Australia
  2. Royal North Shore Hospital, St Leonards, NSW, Australia
  3. University of New South Wales, Kensington, NSW, Australia
  4. Sydney Catalyst Translational Cancer Research Centre , University of Sydney, Camperdown, NSW, Australia
  5. The Jackson Laboratory For Genomic Medicine, Farmington, Connecticut, USA
  6. The University of Texas, M. D. Anderson Cancer Center , Houston, Texas, USA
  7. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  8. Calvary Mater Newcastle, Waratah, NSW , Australia
  9. Prince of Wales Hospital, Randwick, NSW, Australia
  10. UCLA Brain Tumor Imaging Laboratory (BTIL), University of California Los Angeles, Los Angeles, CA, USA
  11. Campbelltown Hospital, Campbelltown, NSW , Australia
  12. Liverpool Hospital, Liverpool, NSW, Australia
  13. Austin Hospital, Heidelberg , VIC, Australia
  14. Royal Brisbane Hospital, Brisbane, QLD, Australia
  15. University of Queensland, , Brisbane, QLD, Australia

BACKGROUND: An increase of mutations as we age is well documented in GBM and in cancer in general. Elderly patients with GBM may have higher mutational burden and may be more likely to respond to immunotherapies. NUTMEG is a randomised Phase II study comparing post radiation NivolUmab and TMZ versus TMZ alone in Elderly patients with newly diagnosed GBM. METHODS: 102 patients will be randomized in a 2:1 allocation to receive short course RT (40Gy/15 daily fractions) and TMZ 75mg/m2) followed by 6 cycles of adjuvant TMZ (150-200mg/m2 days (D) 1-5 q28 days) with Nivolumab (240 mg D1, 15 q28 days for cycles (C) (1-4; 480 mg D1 Q 28 days for C5-6) versus 6 cycles of adjuvant TMZ (150-200mg/m2 D1-5 q28) alone. The study is stratified for ECOG performance status, age (< 70 vs = 70), MGMT methylation and extent of resection. An independent safety monitoring committee is overseeing the trial and will review safety data for the first 10 patients treated on the experimental arm (TMZ + Nivolumab). The primary endpoint is Overall Survival (OS). Secondary endpoints include: 6 month Progression Free Survival, adverse events (AEs) and immune AEs, Quality of life, neurological function (NANO Scale), and correlation of modified RANO and iRANO in the experimental arm. Translational research endpoints include correlation of clinical endpoints with mutational burden, comprehensive immune characteristics and novel MRI sequences including pHweighted MRIs. The expected proportion of patients alive at 24 months is predicted to be 15. 7%. A hazard ratio of more than 0. 69 in favour of the Nivolumab + TMZ arm will be considered sufficient to warrant further investigation including converting this study into a phase III trial. PROGRESS: At 10 August 2018, 8/18 study sites are open in Australia with 8 patients randomized. ACTRN12617000267358.