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May 31, 2014 /PRNewswire/ -- Nektar Therapeutics (NASDAQ: NKTR) announced today new data from an investigator-sponsored Phase 2 study of NKTR-102 (etirinotecan pegol) in patients with Avastin-refractory high-grade glioma conducted at Stanford Cancer Institute under the direction of
Lawrence Recht, M.D., Professor of Neurology and Neurosurgery, with co-investigator
Seema Nagpal, M.D., Clinical Assistant Professor of Neurology and Neurological Sciences, Stanford School of Medicine.
"Patients with Avastin-refractory high-grade glioma currently have little to no treatment options to help them manage their disease," said Dr. Recht. "Patients progress rapidly once resistance develops, objective responses are rarely seen. In this study we saw three patients – 15%, all with glioblastoma - with confirmed partial responses on single-agent NKTR-102 according to RANO criteria and an additional eight patients – 40% -- who had stable disease as a best response."
The trial enrolled 20 patients with high-grade glioma from
August 2012 to May 2013. Patients had a median KPS of 70 and had received a median of three lines of prior therapy, including recurrence following treatment with Avastin. Avastin-refractory was defined as progression by RANO criteria within 60 days of prior Avastin (bevacizumab) treatment. Ninety percent of patients in the trial had glioblastoma. Patients received a median of three cycles (1-22) of NKTR-102 once every three weeks as monotherapy. Six-week progression-free survival in at least 25% of the patients was needed to reject the null hypothesis for the primary endpoint.
Study ResultsThe primary endpoint was met and exceeded with fifty-five percent (95% CI: 31%-75%) of patients in the study achieving six-week progression-free survival. Response and disease progression were assessed by RANO criteria in the trial. Three patients, or 15%, achieved partial responses with NKTR-102 monotherapy with maximum percent reductions in tumor area of 86%, 72%, and 59%. An additional eight patients, or 40%, achieved stable disease as best response. Two of the three patients with RANO responses experienced a long duration of response of 14 and 20 months. Secondary endpoints include median progression-free survival (2.2 months), median survival from time of first NKTR-102 infusion (4.5 months) and median overall survival from date of pathologic diagnosis or confirmation of high-grade glioma (17.1 months). NKTR-102 monotherapy was well-tolerated in patients with Avastin-refractory high-grade glioma with low toxicity in spite of being heavily pre-treated and neurologically symptomatic. Only one patient (5%) had Grade 3 toxicity (diarrhea with dehydration) attributable to NKTR-102 as a result of not taking anti-diarrheal medication. Hematologic toxicity was mild. As of
May 31, 2014, there is one patient in the study who is continuing on NKTR-102 monotherapy.
"Though participants in this trial were heavily pre-treated and more neurologically symptomatic than many clinical trial patients, we observed low toxicity with three partial responses," said Dr. Nagpal. "In addition, two of the three patients with responses experienced a long duration of response of 14 and 20 months, respectively. These results warrant further investigation of NKTR-102 in high-grade glioma, including glioblastoma as single-agent and in combination with bevacizumab, which could theoretically enhance retention of NKTR-102 in the tumor."