The FDA has approved duvelisib (Copiktra) for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or relapsed/refractory follicular lymphoma.
The CLL/SLL indication is a standard approval and the follicular lymphoma indication is an accelerated approval contingent on the results of a confirmatory trial. Both indications are for the treatment of patients who have received at least 2 prior therapies.
The approval is based on data from the phase III DUO trial and the phase II DYNAMO study. In DUO, duvelisib reduced the risk of disease progression or death by 60% versus ofatumumab (Arzerra) in patients with relapsed/refractory CLL/SLL who had received at least 2 prior lines of therapy. The median progression-free survival was 16.4 months with duvelisib versus 9.1 months with ofatumumab (HR, 0.40). In the DYNAMO study, duvelisib demonstrated an overall response rate (ORR) of 42% in patients with follicular lymphoma.
“Copiktra is an important addition to the evolving treatment paradigm for patients with CLL/SLL and follicular lymphoma,” Ian Flinn, MD, PhD, director of the Lymphoma Research Program at Sarah Cannon Research Institute and lead investigator of the DYNAMO and DUO studies, said in a statement.
“The approval of Copiktra for the treatment of relapsed or refractory CLL/SLL after at least two prior therapies, or relapsed or refractory follicular lymphoma after at least two prior systemic therapies, is based on clinical trial data gathered from the treatment of over 400 adult patients. Copiktra is a significant addition to physicians’ treatment armamentarium that I believe will address an unmet need for patients who have limited options once they have progressed after two prior therapies,” added Flinn.
The phase III DUO study randomized 319 patients with CLL/SLL in a 1:1 ratio to duvelisib at 25 mg twice daily until disease progression or unacceptable toxicity, or ofatumumab at 300 mg on day 1, followed by 7 weekly infusions and 4 monthly infusions of 2000 mg.
The FDA based its approval on a subset of these patients with CLL/SLL who had received ≥2 prior lines of therapy. The subset included 95 patients randomized to duvelisib and 101 patients who received ofatumumab. The median patient age across this subset was 69 years (range, 40-90), 88% had an ECOG performance status of 0 or 1, and 59% were male. At baseline, 22% of patients had a detected 17p deletion and 52% had 1 or more tumors ≥5 cm. Over half (54%) of this group had received ≥3 prior treatment lines, with the remaining 46% having received 2.
The median duration of treatment exposure for the duvelisib arm was 13 months (range, 0.2-37). Patients were exposed to ofatumumab for a median duration of 5 months (range, <0.1 to 6). The ORR was 78% with duvelisib versus 39% with ofatumumab.
The follicular lymphoma cohort in the DYNAMO study included 83 patients refractory to rituximab and either chemotherapy or radioimmunotherapy. Sixty-eight percent of patients were male, the median age was 64 years (range, 30-82), and 37% had bulky disease at baseline (target lesion ≥5 cm). Ninety-three percent of patients had an ECOG performance status of 0 or 1.
The median number of prior lines of treatment was 3 (range, 1-10). Ninety-four percent of patients were refractory to their last therapy and 81% were refractory to ≥2 prior lines of therapy. The median length of treatment exposure was 5 months (range, 0.4-24).
The 35 (42%) responders included 1 complete response and 34 partial responses. Forty-three percent of responses were ongoing at 6 months and 17% were maintained at 12 months.
The FDA label for duvelisib includes a Boxed Warning regarding the potential risk of infections, diarrhea or colitis, cutaneous reactions, and pneumonitis in patients receiving duvelisib. According to a press release from Verastem Oncology, the manufacturer of duvelisib, the company is, “implementing an informational Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on Copiktra.”
The company also noted that studies of duvelisib have shown that the most common all-grade adverse events (≥20% occurrence) in patients receiving the drug include diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.
Verastem Oncology Receives FDA Approval of COPIKTRA™ (duvelisib) Capsules. Published September 24, 2018. Accessed September 24, 2018. https://bit.ly/2NDQm80.