A new oral drug for use in patients with certain blood cancers has been approved by the US Food and Drug Administration (FDA).

The drug, duvelisib (Copiktra, Verstem Oncology), is an oral inhibitor of phosphoinositide 3–kinase (PI3K) and is the first to act as a dual inhibitor of PI3K-delta and PI3K-gamma.

The FDA granted approval for use of duvelisib in adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior therapies. This approval was based on data from the DUO trial, which showed a benefit in progression-free survival.

The FDA also granted an accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who had undergone at least two prior systemic therapies. This accelerated approval was based on overall response rate from the DYNAMO clinical trial. Further data showing clinical benefit are required.

These three disorders — CLL/SLL and FL — are common types of indolent non-Hodgkin lymphomas. It is estimated that 681,000 people are living with non-Hodgkin lymphoma in the United States, including nearly 350,000 patients with CLL/SLL or FL, notes the manufacturer. Many of these patients will eventually experience relapse or develop refractory disease, it adds.

The drug has orphan drug designation and was approved after a priority review.

“Duvelisib is an important addition to the evolving treatment paradigm for patients with CLL/SLL and FL,” said Ian Flinn, MD, PhD, director of the Lymphoma Research Program at Sarah Cannon Research Institute. He was lead investigator of the pivotal studies that led to this approval. Together, the studies involved more than 400 patients.

“I believe [it] will address an unmet need for patients who have limited options once they have progressed after two prior therapies,” he said in a company press release.

Boxed Warning and Adverse Effects

The product carries a boxed warning for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. The manufacturer is implementing an informational risk evaluation and mitigation strategy to provide appropriate dosing and safety information to physicians.

The drug is also associated with adverse reactions that may require dose reduction, treatment delay, or discontinuation. These may include infections, diarrhea or colitis, cutaneous reactions, pneumonitis, hepatotoxicity, neutropenia, and embryo-fetal toxicity.

The most common adverse reactions (reported in ≥20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.

Clinical Trial Data

The approval for use in refractory or relapsed CLL/SLL was based on results from a subset of patients who took part in the DYNAMO trial.

This trial compared duvelisib to ofatumumab (Arzerra, Genmab/Novartis) in 319 adult patients with CLL (n = 312) or SLL (n = 7) who had received at least one prior therapy.

The approval was based on a subset of these patients — those who had received at least two prior therapies — because “the benefit:risk appeared greater in this more heavily pretreated population compared to the overall trial population,” the manufacturer explains.

In this subset of patients (95 received buvelisib, 101 received ofatumumab), the median age of the patients was 69 years (range, 40 to 90 years). Among these patients, 46% had received two prior lines of therapy, and 54% had received three or more prior lines.

Efficacy was based on progression-free survival (PFS), as assessed by an independent review committee. The median PFS was 16.4 months with develisib and 9.1 months with ofatumumab (hazard ratio, 0.40).

The accelerated approval for use in patients with previously treated FL was based on the single-arm, multicenter DYNAMO trial, conducted in 83 patients whose conditions were refractory to rituximab and to either chemotherapy or radioimmunotherapy.

This trial excluded patients with grade 3b FL, large cell transformation, prior allogeneic transplant, and prior exposure to a PI3K inhibitor or to a Bruton’s tyrosine kinase inhibitor.

These patients had undergone a median of three prior lines of therapy (range, 1 to 10).

Efficacy was based on overall response rate (35 patients, 42%) and duration of response — 15/35 (43%) maintained the response at 6 months, and 6/35 (17%) maintained the response at 12 months.