NOX66 as monotherapy, and in combination with carboplatin, in patients with refractory solid tumors: Phase 1a/b study

Abstract Background: While oral and intravenous forms of idronoxil have been well tolerated, the safety of NOX66, with idronoxil formulated as a rectal suppository, is not known. This Phase 1a/b clinical study (Protocol No. NOX66-001A), known as Chemotherapy Enhancement Program-1 (CEP-1), is the first to assess NOX66 in patients with refractory solid tumors. Objectives: The study aimed to determine the safety profile of NOX66 both as a monotherapy and in combination with carboplatin, and to evaluate whether NOX66 has a meaningful anti-cancer effect when combined with carboplatin in this patient population. Methods: CEP-1 was a multicenter, open-label, non-randomized, two-dose cohort study of NOX66 as monotherapy (Phase 1a) and in combination with carboplatin (Phase 1b). Patients with refractory solid tumors who had stopped responding to standard treatments were eligible to participate. Twenty patients were screened and 19 enrolled in the study. They were divided into two groups: Cohort 1 (n=8) received one suppository daily (400 mg) and Cohort 2 (n=11) received two suppositories daily (800 mg) for 14 consecutive days followed by 7 days of rest. Patients who completed Phase 1a without significant toxicity continued to Phase 1b, where NOX66 was combined with carboplatin for up to six 28-day treatment cycles, with low dose carboplatin (600 mg) for cycles 1B–3B and standard dose carboplatin (900 mg) for cycles 4B–6B. The main outcomes assessed were safety (n=18) and efficacy signals (n=14). Results: NOX66 generally was well tolerated at 400 mg and 800 mg, both as monotherapy and in combination with carboplatin in patients with refractory solid tumors. The safety profile was consistent for oncology patients, with 77.8% experiencing at least one treatment-emergent adverse event (TEAE). The most common AEs were blood and lymphatic system disorders (44.4%), with only anemia considered to be possibly related to NOX66. While the study was primarily designed to assess safety and tolerability, the efficacy measurements demonstrated that most patients had stable disease or better by study end. Conclusions: The favorable safety profile of NOX66 provides reassurance to justify continuation of clinical research. The efficacy findings are encouraging in terms of the chemosensitizing potential of NOX66 in refractory solid tumors.