NUC-1031 + carboplatin

NUC-1031 + carboplatin is a combination therapy consisting of NUC-1031 (also known as Acelarin), a first-in-class ProTide modification of gemcitabine, and carboplatin, a platinum-based chemotherapy agent. NUC-1031 is designed to overcome cancer drug resistance mechanisms by maximizing intratumoral active metabolites. When combined with carboplatin, this regimen has shown promising efficacy in treating recurrent ovarian cancer, including in platinum-resistant patients. Clinical development included a Phase Ib open-label, dose-escalation study (PRO-002) in recurrent ovarian cancer, which determined a recommended Phase II dose of 500 mg/m² NUC-1031 on days 1 and 8 with AUC5 carboplatin on day 1, administered every 3 weeks. The combination demonstrated encouraging efficacy in heavily pretreated patients, with an objective response rate (ORR) of 26% and a clinical benefit rate (CBR) of 74% across all doses in the Phase Ib study, reaching 100% in the recommended Phase II cohort. Median progression-free survival was 27.1 weeks (approximately 6.6 months). The combination was reported to be well-tolerated, with mild myelosuppression observed at the recommended phase II dose. Pharmacokinetic studies showed NUC-1031 stability in plasma and high intracellular active metabolite levels unaffected by carboplatin.