Publication of Phase 3 Trial Results Supports FDA Approval of Copiktra, Verastem Announces

Publication of Phase 3 Trial Results Supports FDA Approval of Copiktra, Verastem Announces

Copiktra (duvelisib) monotherapy may be an effective and safe treatment option for patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), according to results from a Phase 3 trial now published in a peer-reviewed journal.

Verastem Oncology announced the publication of the study, “The phase 3 DUO trial: duvelisib versus ofatumumab in relapsed and refractory CLL/SLL,” describing the findings from the DUO trial (NCT02004522), in the journal Blood.

These findings, together with previous data from the Phase 2 DYNAMO study (NCT01882803), led to the approval of Copiktra by the U.S. Food and Drug Administration on Sept. 24 for the treatment of patients with CLL/SLL who had undergone at least two prior therapies.

“Continued research for new treatment options is important to address the needs of patients with relapsed or refractory CLL/SLL once they have progressed,” Ian Flinn, MD, PhD, lead investigator of the Phase 3 DUO study and lead author of the paper, said in a press release.

“Duvelisib is an important addition to the evolving treatment paradigm for patients with CLL/SLL and we are delighted to have the study results published in Blood to share with the medical and scientific communities,” said Flinn, who is the director of the Lymphoma Research Program at the Sarah Cannon Research Institute.

Copiktra is an oral inhibitor of phosphoinositide 3-kinase (PI3K) and the first dual inhibitor of PI3K-delta and PI3K-gamma — two enzymes that promote the growth and survival of malignant immune B-cells — to be approved by the FDA.

Copiktra’s new drug application was largely supported by the data obtained from DUO, a randomized, multicenter, open-label Phase 3 trial that compared the safety and efficacy of Copiktra with that of Arzerra (ofatumumab) in 319 patients with CLL/SLL who had received at least one prior therapy.

All patients were randomly divided to receive either 25 mg of Copiktra orally twice a day or Arzerra administered intravenously for seven cycles.

After a median follow-up of 22.4 months, patients on Copiktra had lived significantly longer without signs of disease progression than those receiving Arzerra — 13.3 months vs. 9.9 months. More patients had also responded to Copiktra (73.8%) than to Arzerra (45.3%).

The trial also showed that the treatment benefited patients with high-risk mutations known as a 17p deletion and TP53. These patients had a median progression-free survival of 12.7 months, compared with nine months in those given Arzerra.

The data supporting the approval of Copiktra was based on the efficacy and safety analysis obtained for the majority of heavily pretreated patients (196) participating in DUO who had received at least two different lines of therapy and were at a significantly higher risk in comparison with the remaining patients enrolled in the trial.

Copiktra worked particularly well in this subset, extending the time until disease progression or death from 9.1 to 16.4 months, and showing a higher response rate (78% vs. 39%).

The most common adverse side effects associated with Copiktra were diarrhea (51%), neutropenia (reduced levels of white blood cells; 33%), fever (29%), nausea (23%) and cough (21%). Neutropenia (21%) and infusion reactions (19%) were the most frequent linked to Arzerra.

“Given the unfortunate reality that many patients have or acquire resistance or intolerance to currently-available, targeted therapies, or have comorbidities that may preclude their safe use, there remains a critical medical need for additional, novel, targeted therapies for patients with [relapsed or refractory] CLL/SLL, especially those with del(17p)/TP53 mutations. These combined safety and efficacy results suggest that duvelisib monotherapy may offer an effective treatment for CLL/SLL patients in need of additional therapeutic options,” the researchers wrote in the study.

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