Phase i trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma

Objectives: UNBS5162 is a novel naphthalimide that binds to DNA by intercalation and suppresses CXCL chemokine elaboration. A Phase I study of UNBS5162 was conducted to establish pharmacokinetics (PK), maximum tolerated dose (MTD), dose-limiting toxicity, safety and anti-tumor activity in patients with advanced solid tumors or lymphoma. Methods: UNBS5162 was administered in a 3 + 3 dose escalation scheme by intravenous infusion over 1 h weekly for 3 weeks of a 4-week cycle. Safety, serial serum PK and tolerability were captured throughout the study. Response Evaluation Criteria in Solid Tumors was utilized every 2 cycles to assess for anti-tumor response. Results: Twenty-four patients with metastatic carcinoma and 1 patient with lymphoma were treated at eight dose levels (18-234 mg/m²). All patients were evaluable for tolerability and toxicity. Grade 3 toxicities include nausea (n = 1), fatigue (n = 1) and anorexia (n = 1). Prolongation of QTc [Hodges] was observed in 6 cases (Gr 1 = 2; Gr 2 = 2; Gr 3 = 2). C _max and area under the curve increased linearly with dose with a t _1/2 of 30-60 min. 16 patients completed 2 cycles of therapy, all with pharmacodynamics at 8 weeks. Conclusions: The MTD or dose-limiting toxicity for UNBS5162 was not reached due to the magnitude of QTc prolongation at the highest dose of 234 mg/m²/week that led to study termination.