Phase I trial of UNBS5162, a novel naphthalimide in patients with advanced solid tumors or lymphoma.
OBJECTIVE
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/m(2)). 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/m(2)/week that led to study termination.
Arizona Cancer Center, Tucson, AZ, USA, dmahadevan@westclinic.com.
Daruka
D
Mahadevan
Donald W
DW
Northfelt
Pavani
P
Chalasani
Diane
D
Rensvold
Sandra
S
Kurtin
Daniel D
DD
Von Hoff
Mitesh J
MJ
Borad
Raoul
R
Tibes
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology*; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D051379:Mice; D008875:Middle Aged; D053644:Naphthalimides / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051381:Rats; D014508:Urea / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D053644:Naphthalimides; C531082:UNBS 5162; D014508:Urea