A phase I/II trial of NOX66 in combination with nivolumab in patients (pts) with advanced cancer

e14591 Background: NOX66 (idronoxil) targets ENOX2 and suppresses STING-mediated inflammatory pathways, reducing IFN and NFκB driven cytokine production by cancer cells. Adding NOX66 to nivolumab may help overcome resistance mechanisms to checkpoint inhibitors and improve responses in patients. Methods: IONIC-1, is an open label Phase I/II trial evaluating safety and preliminary efficacy of NOX66 (suppositories daily x 1 week, then 1 week rest) combined with nivolumab (240mg IV every 2 weeks). Three dose cohorts of NOX66 are planned (1200mg daily, 1800mg daily, 2400mg daily). Objectives include safety, tolerability, and clinical and radiological responses. Two groups are being studied: 1) Pts who have prior progression on a checkpoint inhibitor; 2) Pts naïve to checkpoint inhibitors. Results: 11 pts have been treated to date; 3 in Group 1, and 8 in Group 2. All pts have received at least 2 cycles of the combination treatment; 2 pts completed 8 cycles, and 2 pts remain on study. Tumour types include lung, prostate, gastric, pancreatic, nasopharyngeal and metastatic squamous carcinoma. Early signals of tumour response based on RECIST 1.1 criteria include stable disease in 2 pts (SD at 8 weeks and at 16 weeks); partial response (PR) in 1 patient at 16 weeks; complete response (CR) in 2 pts, both with ongoing CR at 24 weeks. Five pts had disease progression, and 1 pt was withdrawn due to suspected immune mediated myositis and hepatitis resulting from nivolumab and was not evaluable. The most common AE was local perineal irritation, readily managed with topical corticosteroid cream. Two pts developed an erythematous rash over the trunk and limbs after 2 cycles, suspected to be related to the combination treatment. Using a 32 multiplexed immune cytokine assay to evaluate the single-cell functional states of CD4+ and CD8+ T cells in patients’ peripheral blood mononuclear cells (PBMCs) at pre-treatment and at Cycle 3 Day 1, we found a significant increase in polyfunctionality in both effector CD4+ and CD8+ve T cells compared to baseline in responder patients. Conclusions: Preliminary analysis shows promising tumour responses from the combination therapy which appears to be well-tolerated, with no safety signals evident to date. Clinical trial information: ACTRN12621001537842 .