Nektar Therapeutics presented favorable data today from a phase I study of etirinotecan pegol (EP, NKTR-102) in combination with 5-fluorouracil (5-FU)/Leucovorin (LV) in patients with advanced cancer. NKTR-102 is the first long-acting topoisomerase I-inhibitor designed to concentrate in tumor tissue, provide sustained tumor suppression throughout the entire chemotherapy cycle, and to reduce the peak exposures that are associated with toxicities of other cytotoxics.

"Topoisomerase I inhibition combined with 5-FU and LV remains one of the most active combinations used in advanced colorectal cancer. NKTR-102, a long-acting topoisomerase I-inhibitor, was safely combined with 5-FU/LV, and showed signs of clinical benefit including both objective responses and tumor marker reductions," said Ramesh K. Ramanathan, M.D., Virginia G. Piper Cancer Center, Scottsdale and clinical professor of medicine, College of Medicine- Phoenix Campus, University Arizona and a PI of the trial. "Continued development using this promising long-acting topoisomerase combination therapy is warranted, especially in clinical trials for advanced gastrointestinal malignancies."

The phase I study assessed the safety, pharmacokinetics and anti-tumor activity of NKTR-102 when given in combination with standard doses of 5-FU/LV. Data was presented from 26 patients enrolled in five cohorts in a standard dose escalation design.

The study established a recommended dose of 75mg/m NKTR-102 in combination with standard doses of 5-FU/LV given every two weeks.  Promising clinical activity, including objective response (2 patients), clinical benefit (stable disease>=6 months; 10 patients) and clinically significant declines in tumor markers were observed (including a patient with pancreatic cancer whose disease had progressed on prior irinotecan). Toxicities of diarrhea and reversible neutropenia were generally manageable with dose delays and reductions.