CHICAGO―The oral targeted agent idelalisib (GS-1101) is associated with rapid tumor response in some patients diagnosed with relapsed or treatment-resistant chronic lymphocytic leukemia (CLL), according to results of a phase 1 clinical trial presented at the 2013 American Society of Clinical Oncology (ASCO) Annual Meeting.

“Idelalisib shows substantial clinical activity and a favorable safety profile in heavily pretreated, refractory and high-risk patients with CLL,” reported lead author Jennifer Brown, MD, PhD, of the Dana-Farber Cancer Institute in Boston, MA.

Idelalisib is the first selective inhibitor of PI3K-delta. The reported trial represents the first study of a PI3K inhibitor among patients with CLL.

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Most of the 54 participants (83%) in the study were males. Half of 54 patients exhibited rapid tumor shrinkage, with a median time to first response of 1.9 months (range, 0.9-12.9 months), Dr. Brown noted. Nodal responses were noted at all dose levels, she said.

Mean delayed disease progression time was 17 months. Patients had undergone an average of five prior lines of therapy.

Treatment had to be discontinued in 13 (24%) patients: eight (15%) as a result of disease progression. Pneumonia, febrile neutropenia, infections, and renal failure also contributed to discontinuation in six patients.

No dose-limiting toxicities occurred, Dr. Brown said. Serious adverse events occurring in two or more patients included pneumonia in 10 (19%) patients, febrile neutropenia in five (9%), and cellulitis and colitis (three each [6%]).

The most common adverse events overall were fatigue (31%; grade 3+, 2%), diarrhea (30%; grade 3+, 6%), pyrexia (30%; grade 3+, 4%), cough (24%; grade 3+, 4%), rash (22%; grade 3+, 0%), upper respiratory tract infection (22%; grade 3+, 0%), back pain (22%; grade 3+, 0%), URI (22%; grade 3+, 0%), and pneumonia (20%; grade 3+, 19%), Dr. Brown reported.

Phase 3 trials of idelalisib plus rituximab or bendamustine/rituximab are under way, Dr. Brown noted (NCT01539512, NCT01569295).

“We are reaching a point in CLL where we have multiple agents in development that are very effective,” Dr. Brown said.

“This study illustrates how our growing understanding of tumor biology enables development of highly active and promising targeted drugs,” commented ASCO President Sandra Swain, MD, FACP. “It also offers a glimpse of the possibility of a new, chemotherapy-free alternative for chronic blood cancers.”

The study was supported by Gilead Sciences.