General Information

Copiktra (duvelisib) is a dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells.

Copiktra is specifically indicated for the following:

the treatment of adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma after at least two prior therapies

the treatment of adults with relapsed or refractory follicular lymphoma after at least two prior systemic therapies

Copiktra is supplied as a capsule for oral administration. The recommended dose is 25 mg administered as oral capsules twice daily (BID) with or without food. A cycle consists of 28 days. The capsules should be swallowed whole. The capsules should not be opened, broken, or chewed. If a dose is missed by fewer than 6 hours, take the missed dose right away and take the next dose as usual. If a dose is missed by more than 6 hours, wait and take the next dose at the usual time. See drug label for specific dose modifications due to adverse reactions.

Mechanism of Action

Copiktra (duvelisib) is an inhibitor of PI3K with inhibitory activity predominantly against PI3K-δ and PI3K-γ isoforms expressed in normal and malignant B-cells. Duvelisib induced growth inhibition and reduced viability in cell lines derived from malignant B-cells and in primary CLL tumor cells. Duvelisib inhibits several key cell-signaling pathways, including B-cell receptor signaling and CXCR12-mediated chemotaxis of malignant B-cells. Additionally, duvelisib inhibits CXCL12-induced T cell migration and M-CSF and IL-4 driven M2 polarization of macrophages.

Side Effects

Adverse effects associated with the use of Copiktra may include, but are not limited to, the following:

diarrhea or colitis

neutropenia

rash

fatigue

pyrexia

cough

nausea

upper respiratory infection

pneumonia

musculoskeletal pain

anemia

The Copiktra drug label comes with the following Black Box Warning: Fatal and/or serious infections occurred in 31% of Copiktra treated patients. Monitor for signs and symptoms of infection. Withhold Copiktra if infection is suspected. Fatal and/or serious diarrhea or colitis occurred in 18% of Copiktra-treated patients. Monitor for the development of severe diarrhea or colitis. Fatal and/or serious cutaneous reactions occurred in 5% of Copiktra-treated patients. Fatal and/or serious pneumonitis occurred in 5% of Copiktra-treated patients. Monitor for pulmonary symptoms and interstitial infiltrates.

Indication 1 - relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

approved September 2018

Clinical Trial Results

The FDA approval of Copiktra for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma was based on the phase III DUO study. The study enrolled 319 patients who were randomized 1:1 to receive either duvelisib 25mg orally twice daily or ofatumumab monotherapy, an approved standard of care treatment for use in CLL/SLL, per its label with an initial infusion of 300 mg followed by 7 weekly infusions and 4 monthly infusions of 2,000 mg. The DUO study met its primary endpoint with oral duvelisib monotherapy achieving a statistically significant improvement in median PFS (mPFS) compared to ofatumumab in per a blinded Independent Review Committee using iwCLL or revised IWG Response Criteria (modified iwCLL/IWG; 13.3 months vs 9.9 months, respectively), representing a 48% reduction in the risk of progression or death.

Indication 2 - relapsed or refractory follicular lymphoma

approved September 2018

Clinical Trial Results

The FDA approval of Copiktra for relapsed or refractory follicular lymphoma was based on the DYNAMO study. The study enrolled 129 patients with iNHL who were refractory to rituximab (Rituxan) and either chemotherapy or radioimmunotherapy. Among the 129 enrolled patients, the disease types included follicular lymphoma (n = 83), SLL (n = 28), and marginal zone lymphoma (n = 18). Continuous duvelisib was administered at 25 mg twice daily. In the DYNAMO study, duvelisib demonstrated an overall response rate of 46% for patients with iNHL, including 41% in patients with follicular lymphoma.