Therapeutic efficacy of Idelalisib

Idelalisib was evaluated in Study 312-0116, a randomized, double-blind, placebo-controlled trial involving 220 patients with relapsed chronic lymphocytic leukemia who required treatment and were unable to tolerate standard chemoimmunotherapy due to comorbid medical conditions, reduced renal function, or grade 3 or higher neutropenia or grade 3 or higher thrombocytopenia resulting from the myelosuppressive effects of prior cytotoxic drug therapy. Patients were randomized 1:1 to receive up to 8 doses of rituximab in combination with oral placebo twice daily or idelalisib 150 mg orally twice daily until disease progression or unacceptable toxicity occurred.

The median age was 71 years, with 78% over 65 years old, 66% male, and 90% White. The median time since diagnosis was 8.5 years. The median number of prior treatment lines was 3. Almost all patients had received anti-CD20 monoclonal antibody therapy. The most common prior treatment regimens were bendamustine plus rituximab, fludarabine plus cyclophosphamide plus rituximab, rituximab monotherapy, fludarabine plus rituximab, and chlorambucil. The median Cumulative Illness Rating Scale score was 8, with 85% of patients having a score greater than 6. The median Karnofsky Performance Status score was 80. The median estimated creatinine clearance was 63.6 mL/min, with 41% of patients having an estimated creatinine clearance of less than 60 mL/min. At screening, 19.5% of patients had a platelet count of less than 50×10^9/L, and 13.2% had an absolute neutrophil count of less than 1×10^9/L.

The efficacy of idelalisib was based on progression-free survival as assessed by an Independent Review Committee. The trial was stopped early for efficacy after the first prespecified interim analysis. Results from the second interim analysis continued to demonstrate a statistically significant improvement in the primary efficacy outcome measure of progression-free survival with idelalisib plus rituximab compared with placebo plus rituximab.

At the final analysis, the median progression-free survival was 19.4 months in the idelalisib plus rituximab group versus 6.5 months in the placebo plus rituximab group.

Summary of efficacy results: The median progression-free survival was 19.4 months in the idelalisib plus rituximab group versus 6.5 months in the placebo plus rituximab group. The overall response rate was 83.6% in the idelalisib plus rituximab group versus 15.5% in the placebo plus rituximab group. The median duration of response was not reached in the idelalisib plus rituximab group versus 6.2 months in the placebo plus rituximab group.

FDA，2022.02