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.