Final results of a phase I dose-escalation study of ON 01910.Na in combination with oxaliplatin in patients with advanced solid tumors.

Abstract

e13584 Background: ON 01910.Na is a novel multitargeted inhibitor of several regulatory pathways including polo-like kinase 1 (Plk1) and PI-3 kinases, with synergistic nonclinical activity when combined with oxaliplatin, prompting phase I clinical evaluation. Methods: Patients with advanced cancer received escalating doses of ON 01910.Na as 24hr weekly continuous infusions. Oxaliplatin was administered biweekly as a 85mg/m2, 2 hr infusion. The ON 01910.Na dose cohorts ranged from 250-1,350 mg/m2 based on a modified Fibonacci escalation algorithm using the accelerated titration scheme (NCI). Intrapatient dose escalation was allowed. Results: Thirty patients (pts) (22 females; ages: 29-80 yrs received an overall mean 9.4 (range=1-30) number of weeks of combination therapy: ON 01910.Na mg/m2: 250 n=10; 650 n=9; 1,050 n=8; 1,350 n=3. No dose-limiting toxicity was observed in any patient. Grade 3+ toxicities included pain (3 pts), lethargy and weakness (1 pt), pneumonia (1 pt), hyponatremia (1pt), anemia (1pt), transient ischemic attack (1pt), vomiting (1pt), urinary tract infection (1pt), shortness of breath and myocardial infarction (1pt). Confirmed partial response was observed in 1 pt with chemotherapy- refractory ovarian cancer (duration = 11 wks) and in another pt with metastatic breast cancer (duration = 13 wks). Stable disease was observed in 4 pts with colon cancer (42 wks and 12 wks), ovarian and renal cancer (12 wks). Conclusions: ON 01910.Na administered as a 24hr infusion in combination with oxaliplatin was well tolerated and resulted in objective tumor responses in advanced ovarian, breast, colon and renal cancer.