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

Daruka Mahadevan, Donald W. Northfelt, Pavani Chalasani, Diane Rensvold, Sandra Kurtin, Daniel D. Von Hoff, Mitesh J. Borad, Raoul Tibes

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)934-941
Number of pages8
JournalInternational Journal of Clinical Oncology
Volume18
Issue number5
DOIs
StatePublished - Oct 2013

Keywords

  • Chemokines
  • Dose-limiting toxicity
  • Maximum tolerated dose
  • Naphthalimide
  • QTc

ASJC Scopus subject areas

  • Surgery
  • Hematology
  • Oncology

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