Based on progression-free survival data, a single-arm, open-label phase IIa study of Asonep in metastatic renal cell carcinoma will be extended to a second cohort.
The decision followed an interim analysis of RCC patients that have failed at least one therapy involving a VEGF inhibitor and no more than one mTOR inhibitor, with a maximum of three failed treatments in all. This patient population is considered “last line,” and the literature suggests cancer progression in this population within a one-to-two month time frame, according to Asonep’s sponsor, Lpath Inc.
Lpath has enrolled 26 patients in the study. Asonep has a favorable safety profile thus far, with no drug-related serious adverse events.
The first 17 patients were initiated at a dose of 15 mg/kg. Of these, seven had progressive disease at or before the end of four months; eight were progression-free at the four-month mark—with one of these patients deemed a partial responder, and three experiencing reduced tumor volume, but not enough to be categorized as a partial responder. Two exited the study due to serious adverse events unrelated to the drug prior to the four-month mark, and are not considered evaluable.
Notably, of the eight patients that were stable or better as of the fourth month, two are now in month 15 of the study, one is in month 13, and one is in month 10. An additional patient was stable through month seven, but then missed six treatments during a vacation, and shortly thereafter progressed.
The next nine patients were initiated at a dose of 24 mg/kg. Of these higher-dose patients: four had progressive disease at or before the end of four months; two were progression-free at the four-month mark (with one deemed a partial responder); and the remaining three have not yet reached their four-month mark.
“A bimodal distribution of patients has emerged, whereby half the patients experience disease progression early, consistent with their ‘last line’ prognosis, while the other half experience stable disease, with a number of them still progression-free beyond one year,” said Dario Paggiarino, Lpath chief development officer. “Based on the safety profile and the promising results, we have moved beyond the first cohort of 22 evaluable patients into a second cohort, allowing us to enroll up to a total of 54 evaluable patients.”
Lpath says it will consider studying Asonep in RCC patients as a first-line or second-line treatment in combination with other drugs, as well as in patients with other tumor types, either in combination or as a single agent. This trial has been partially funded by a $3 million grant from NCI under its Small Business Innovation Research Program.
