A first-in-class investigative drug targeted to the P13K pathway was active in a phase-I study of 54 heavily pretreated patients with chronic lymphocytic leukemia.
The new oral drug, called idelalisib (GS-1101), selectively blocks PI3K-delta and produced "rapid and long-lasting tumor shrinkage in half (2 complete responses and 28 partial responses) of the patients treated with single-agent therapy, stalling disease progression for 17 months, on average. The activity of the drug is noteworthy, given that the patients had already undergone an average of five prior therapies," Dr. Jennifer R. Brown reported during a press conference sponsored by the American Society of Clinical Oncology that featured key research to be presented at its upcoming annual meeting.
Dr. Jennifer R. Brown
Most symptomatic patients with chronic lymphocytic leukemia (CLL) experience a relapse at some point after initial chemoimmunotherapy. About 20% of them relapse within 6 months or do not respond to initial treatment and need better treatments, noted Dr. Brown of the Dana-Farber Cancer Institute, Boston.
"While this research is still early and ongoing, we hope this drug, along with others like it, will lead to prolonged survival and eventually help turn CLL into a condition that is treated like high blood pressure, where a patient can take a couple of pills every day. In the shorter term, these drugs may also provide an alternative to chemotherapy in elderly patients who tend not to tolerate chemotherapy well," she said.
Phase-III trials of idelalisib are under way with a 150-mg, twice-daily dosing schedule, Dr. Brown said.
She reported that the current trial included 54 patients (9 women and 45 men, ranging from 37 to 82 years of age) with bulky lymphadenopathy (80%), refractory disease (70%), and a median of 5 prior treatments (range, 2-14). They were treated continuously with single-agent oral idelalisib at doses ranging from 50 to 350 mg/dose on either a once- or twice-daily schedule for an average duration of 9 months (range, 0-42).
The objective response rate was 56% (2 complete responses and 28 partial responses). At least a 50% reduction in the nodal SPD (sum of the products of the greatest perpendicular diameters) was seen in 44 (81%). Splenomegaly resolved in 14 of 20 affected patients (70%) and cytopenias normalized in 17 of 25 (68%) with anemia, 27 of 34 (79%) with thrombocytopenia, and all 15 patients with neutropenia (100%), Dr. Brown reported.
The most common adverse events of grade 3 or higher, independent of causality, included fatigue (2%), diarrhea (6%), pyrexia (4%), pneumonia (19%), and ALT/AST elevation (2%). Treatment was discontinued because of adverse events in 15% (7% potentially treatment related). There were no dose-limiting toxicities.
The research was supported by Gilead Sciences.
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