Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2018

A Phase 2 trial of durvalumab and tremelimumab with chemotherapy in metastatic EGFR mutant non-small cell lung cancer following progression on EGFR tyrosine kinase inhibitors (ILLUMINATE) (#417)

Chee Khoon Lee 1 2 , Antony Mersiades 1 , Jenna Mitchell 1 , Chris Brown 1 , Hannora Jurkovic 1 , Ben Solomon 3 , Thomas John 4 , Martin Stockler 1 , James Chi-Hsin Yang 5
  1. NHMRC Clinical Trials Centre, University of Sydney, Camperdown, NSW, AUSTRALIA
  2. Department of Medical Oncology, St George Hospital, Sydney, NSW, Australia
  3. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia
  4. Department of Medical Oncology, Olivia Newton John Cancer Centre, Melbourne, VIC, Australia
  5. National Taiwan University Hospital, Taipei, Taiwan


Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an established standard of care for treatment for advanced EGFR mutant non-small cell lung cancer (NSCLC), but the emergence of drug resistance is universal, and outcomes with subsequent platinum-pemetrexed chemotherapy are poor.  The role of immune-checkpoint inhibitor monotherapy in EGFR mutant NSCLC remains uncertain with trials demonstrating inferior survival outcomes as compared with chemotherapy. However, a recent randomized study of combination checkpoint inhibitor-chemotherapy has demonstrated improved survival over chemotherapy in this patient population.  This study aims to evaluate the efficacy and tolerability of combination dual immune-checkpoint blockade, durvalumab and tremelimumab, with platinum-pemetrexed in metastatic EGFR mutant NSCLC following progression on EGFR-TKIs.


This international phase 2 trial with two cohorts will recruit 100 patients from Australia and Taiwan with advanced EGFR mutant NSCLC following disease progression with EGFR-TKI therapy.  Cohort 1 (n=50) will enrol patients with no evidence of T790M mutation on tissue or plasma.  Cohort 2 (n=50) will enrol patients with a T790M mutation; patients will be required to have prior 3rd generation TKI therapy.  Patients will receive 4 cycles of induction durvalumab (1500mg) and tremelimumab (75mg) with platinum-pemetrexed chemotherapy every 3 weeks followed by maintenance durvalumab with pemetrexed until disease progression.  Major endpoints include objective tumour response rate (OTRR; RECIST1.1; primary), disease control rate, OTRR (iRECIST), progression-free survival, overall survival, and adverse events.  Correlative studies including PD-L1 expression, tumour mutational burden and plasma cell-free DNA are planned.  Response will be assessed 6 and 12 weeks, then every 8 weeks during the first year, then every 12 weeks.

ILLUMINATE is an investigator-initiated, cooperative-group trial led by the Australasian Lung Cancer Trials Group in collaboration with the National Taiwan University Hospital and the NHMRC Clinical Trials Centre, University of Sydney.