Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have proven remarkably effective in the treatment of advanced EGFR mutant non-small cell lung cancer (NSCLC). However, drug resistance is inevitable 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 compared to chemotherapy. However, a recent randomised study with combination checkpoint inhibitor-chemotherapy demonstrated improved survival over chemotherapy alone 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 chemotherapy in metastatic EGFR mutant NSCLC following progression on EGFR-TKIs. Methods: This international phase II cohort study will recruit 100 participants from Australia and Taiwan with advanced EGFR mutant NSCLC following disease progression with EGFR-TKIs [Cohort 1 (n=50): T790M mutation negative on tissue and plasma; Cohort 2 (n=50): T790M mutation positive on tissue and/or plasma, and progression on3^rd generation TKIs]. Participants will receive 4 cycles of induction durvalumab 1500mg and tremelimumab 75mg with platinum-pemetrexed chemotherapy every 3 weeks, followed by maintenance durvalumab 1500mg and pemetrexed 500mg/m2 every 4 weeks until disease progression. Response will be assessed at 6 and 12 weeks, then 8-weekly during the first year, and 12-weekly thereafter. 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 include biomarker assessment as potential predictive/prognostic factors. ILLUMINATE is a collaboration between the Australasian Lung Cancer Trials Group, National Health Research Institutes (Taiwan) and the NHMRC Clinical Trials Centre, University of Sydney. As of 6/2/2020, 11 of planned 100 participants have been recruited. Clinical trial information: NCT03994393.