News Feature | January 23, 2014

Nektar Presents Positive Clinical Data On Etirinotecan Pegol With 5-Flourouracil/Leucovorin

Source: Clinical Leader

By Cyndi Root

Nektar Therapeutics announced via a press release that a Phase I study of a new cancer drug combination has produced positive results. Etirinotecan pegol (EP, NKTR-102) in combination with 5-fluorouracil (5-FU)/Leucovorin (LV) produced tumor suppression throughout the chemotherapy lifecycle. NKTR-102 is a topoisomerase I-inhibitor engineered to concentrate in tumor tissue and reduce toxicities from other drugs. The data from the trial was presented at the 2014 Gastrointestinal Cancers Symposium in San Francisco, California.

Ramesh K. Ramanathan, M.D., principal investigator said, "Topoisomerase I inhibition combined with 5-fluorouracil (5-FU) and leucovorin (LV) remains one of the most active combinations used today 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.” He added that further development and clinical trials are warranted and hold promise for advanced gastrointestinal malignancies.

Gastrointestinal Malignancies

Gastrointestinal cancer is cancer of the digestive system. Malignancies can invade the liver, stomach, esophagus, small and large intestine, gallbladder, rectum, and colon. About 20 percent of new cancer cases or 250,000 annually are gastrointestinal. When cells in the gastrointestinal system divide in an uncontrolled way, they can form malignant tumors.  Abnormal cells often spread to healthy cells and migrate to nearby organs or to nearby lymph glands, spreading throughout the body.

The Phase I Study

Researchers conducted the Phase I study to assess the pharmokinetic profile, anti-tumor activity, and safety of the drug combination. Twenty-six patients were organized into five cohorts in a trial design of standard dose escalation. Researchers established an effective dose of 75 mg/m2 NKTR-102 in combination with standard doses of 5-FU/LV. The drug combination was administered every two weeks.

Study authors observed positive findings in several areas. Two patients had a partial or complete response (shrinking tumor), 10 patients experienced a stabilized response for six months, and tumor markers decreased significantly. Of note, a pancreatic cancer patient’s tumor markers decreased. Side effects and toxicities with symptoms of neutropenia and diarrhea were managed with dose reductions and delays.

Etirinotecan pegol (EP, NKTR-102) is thought to penetrate the environment of the tumor through the vasculature, thereby increasing the concentration of the drug. The drug’s profile allows it to provide a steadier course of action, rather than action peaks that increase toxicity. Researchers are investigating the drug for other types of cancer including lung and ovarian cancer.

 

Source:
http://ir.nektar.com/releasedetail.cfm?ReleaseID=820036