FDA Approves Duvelisib for the Treatment of Certain Adults with CLL or SLL

The US Food and Drug Administration (FDA) has approved Verastem, Inc.’s duvelisib (COPIKTRA) for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least 2 prior therapies.

An accelerated approval was also granted to duvelisib for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) following at least 2 prior systemic therapies.

The decision to approve the CLL and SLL indication was based on a randomized, multicenter, open-label phase 3 trial comparing the safety and efficacy of duvelisib with ofatumumab in patients with relapsed or refractory CLL or SLL.

For the trial, patients were randomized (1:1) to receive either oral duvelisib 25 mg twice-daily or an intravenous infusion of ofatumumab to be administered at an initial dose of 300 mg, followed 1 week later by 2000 mg once-weekly for 7 doses, and then 2000 mg once every 4 weeks for 4 additional doses, according to the FDA. The analysis included a total of 196 patients who had received at least 2 prior therapies—95 were randomized to receive duvelisib, while 101 would receive ofatumumab.

The estimated median progression-free survival—as assessed by an independent review committee (IRC)— was 16.4 months in the duvelisib arm and 9.1 months in the ofatumumab arm (hazard ratio of 0.40; standard error 0.2). The overall response rate (ORR) per IRC for the duvelisib and ofatumumab arms was 78% and 39%, respectively (39% difference, standard error 6.5%).

A single-arm multicenter trial of duvelisib enrolling 83 patients with FL who were refractory to rituximab and to either chemotherapy or radioimmunotherapy served as the basis for the accelerated approval of the FL indication.

The IRC determined the ORR, which was 42% (95% CI: 31, 54). Forty-one percent of patients experienced partial responses and 1 patient experienced a complete response. For at least 6 months, 15 of the 35 respondents (43%) maintained responses, while 6 (17%) maintained responses for at least 12 months. The FDA notes that continued approval for this indication will be dependent on if the clinical benefit of the treatment is supported in a planned randomized trial.

Fatal and/or serious infections, diarrhea or colitis, cutaneous reactions, and pneumonitis and warnings for neutropenia and hepatotoxicity include boxed warnings with duvelisib. Serious adverse reactions were experienced by 65% of 442 patients with hematologic malignancies who had been treated with duvelisib at the approved dose. Infection, diarrhea or colitis, and pneumonia were noted as the most frequent serious treatment-associated adverse reactions.

Diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia were listed as the most common treatment-related adverse reactions (incidence ≥ 20%).

Permanent discontinuation of duvelisib occurred in 35% of patients due to adverse reactions, and dose reduction occurred in 24% of patients.

The recommended dose for treatment with duvelisib is orally, at 25 mg, twice-daily; it should be taken continuously in 28-day treatment cycles.