The isoflavone idronoxil has been shown to be an effective chemosensitizing agent across various tumour cell lines, with its selective inhibition of tumour specific NADH oxidase (ENOX2) identifying it as a prime drug candidate. Clinical trials of oral idronoxil, however, showed no clinical efficacy, due to rapid and complete Phase 2 metabolism and elimination of idronoxil. NOX66 is a formulation of idronoxil within a fatty acid base which, when delivered rectally, may protect idronoxil from complete Phase 2 metabolism and rapid elimination. Here we will present interim results from the first human study, discussing the safety of NOX66 at two doses and inital efficacy findings of low dose NOX66 in combination with low dose carboplatin.
Patients (16) with end stage, refactory solid tumours, and no further therapy options available, were allocated to one of two treatment cohorts, receiving NOX66 at a dose of 400mg or 800mg of idronoxil daily. Part 1: Patients receive NOX66 for 14 consecutive days as monotherapy, to assess idronoxil levels and safety of monotherapy. Following saftey assessment, each patient through to Part 2. Part 2: Patients receive NOX66 in combination with carboplatin for up to 6 treatment cycles of 28 days. NOX66 is administered on days 1-7 of each cycle, with carboplatin on Day 2. Carboplatin is initially administered at low dose (AUC4), increasing to standard dose (AUC6) following the completion of 3 cycles. Ongoing safety are conducted throughout the study, with measures to identify efficacy signals (CT scan, ECOG) performed at baseline and after Cycles 3 and 6.
Recruitment for the study was completed in September 2017. As of October 2017, there have been no adverse events associated with NOX66 that have led to study discontinuation. Cohort 1, Low dose (AUC4) carboplatin treatment with NOX66 (400mg) has completed, with 5 of the 8 patients reporting Stable Disease and one patient reporting Disease Progression. Two patients could not be evaulated (1 withdrawal, 1 non-evaluable lesion).
NOX66 in combination with carboplatin is well tolerated, with efficacy data for patients receiving low dose-low dose combination therapy providing evidence to suggest that NOX66 may sensitize end stage solid tumours to chemotherapy.
Clinical trial identification
Protocol NOX66-001A; NCT02941523
Legal entity responsible for the study
G. Kelly, I. Minns: Employee of the sponsor organization, Noxopharm Limited. M. Messina: Employee and shareholder of the sponsor company, Noxopharm Limited.