Safety and Efficacy of NOX66 in combination with Nivolumab for patients with solid tumours – a pilot study (IONIC-1).

This is a phase I/II, open-label, non-randomised study of NOX66 in patients with solid tumours who can also be treated with nivolumab. Two groups of participants will be recruited to the study and will be enrolled in parallel with a total of 30 participants: - Group 1: Patients who are already receiving a checkpoint inhibitor and have minor disease progression. The current checkpoint inhibitor will be switched to nivolumab and NOX66 will be added. The study aim in the first group is to determine whether the addition of NOX66 to nivolumab specifically can convert a non-response to checkpoint inhibitors into a response. - Group 2: Patients with minor progression on chemo- or targeted therapy and with tumour types that may not respond to nivolumab alone. These patients will be naïve to checkpoint inhibitors. After 1 cycle of NOX66 monotherapy, patients will be treated with the combination therapy – NOX66 and nivolumab. The study aim in the second group is to determine whether patients will respond to the combination treatment. Within each group there will be dose escalation of NOX66 and dose expansion. Three doses of NOX66 will be evaluated during the dose escalation phase of the study. The first 3 patients in each group will receive the lowest dose level, 1200mg. The second and third anticipated dose levels are 1800mg and 2400mg, respectively. Safety data in each group will be assessed after 3 patients have completed 1 cycle of combination treatment (NOX66 plus nivolumab). In Group 1, this will occur after 3 patients have completed 1 x 14 day cycle. In Group 2, this will occur after 3 patients have completed 2 x 14 day cycles. Patients will remain on their assigned NOX66 dose level for the duration of the study. Data from the dose escalation phase will determine the dose used in the dose expansion phase. In dose expansion, the highest NOX66 dose that is safe and well tolerated will be assigned to the remaining patients in each group. NOX66 is formulated as a suppository and will be rectally administered on Days 1 to 7 of each cycle, with a NOX66–free period from Days 8 to 14. A cycle duration is 14 days. Compliance will be assessed at each cycle and patients will be required to complete a paper dosing diary. Nivolumab (240 mg) will be given intravenously on Day 1 of each cycle, starting at either Cycle 1 (in Group 1) or Cycle 2 (in Group 2). The nivolumab dose will be fixed during the study unless dose delay or discontinuation is required. Combination treatment will continue until disease progression, unacceptable toxicity, consent withdrawal or study completion. Patients will be administered nivolumab and NOX66 for a maximum period of 2 years.