Copiktra Induces Promising Clinical Activity in PTCL Patients, Phase 1 Trials Show

Copiktra (duvesilib) shows promising clinical activity in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL), inducing responses in 44% to 57% of patients included in Phase 1 trials.

The findings were presented during an oral presentation, “Duvelisib, an oral dual PI3K‐δ,γ inhibitor, efficacy and safety in patients with relapsed or refractory (RR) peripheral T‐cell lymphoma: rationale for the Phase 2 PRIMO trial,” at the 2019 International Conference on Malignant Lymphoma (ICML), held recently in Lugano, Switzerland.

Copiktra, developed by Verastem Oncology, is an oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma — two enzymes that promote the survival and growth of malignant B- and T-cells.

It was the first oral dual inhibitor to be approved by the U.S. Food and Drug Administration for the treatment of patients with relapsed of refractory chronic lymphocytic leukemia, small lymphocytic lymphoma, or follicular lymphoma who had received at least two prior therapies.

At the conference, Verastem presented the findings of two open-label Phase 1 trials (NCT01476657; NCT02783625) assessing the safety and pharmacokinetic properties of Copiktra in patients with relapsed or refractory PTCL. Pharmacokinetics is the study of how a drug is absorbed, distributed, metabolized, and eliminated from the body.

In one of the trials, 13 patients were treated with Copiktra at a dose of 75 mg twice a day until disease progression or therapy intolerance, as part of a dose-escalation phase. In the second trial, 16 patients were treated with Copiktra at a dose of 25 mg or 75 mg, twice a day, for one month, as a lead-in to a combination therapy with Istodax (romidepsin) or Velcade (bortezomib).

Key findings from both studies presented at the conference showed that:

• Patients who received Copiktra alone at a dose of 75 mg achieved an overall response rate of 54%, including 15% complete responses.
• Patients given 75 mg of Copiktra as a lead-in monotherapy before Istodax, achieved an overall response rate of 44%, including 22% complete responses.
• Patients who were treated with 25 mg of Copiktra as a lead-in treatment before Velcade, achieved an overall response rate of 57%.
• Patients participating in the dose-escalation trial responded to Copiktra at the second treatment cycle, while those receiving Copiktra as a lead-in treatment started responding at the end of the first cycle of treatment.
• The time patients lived without their disease worsening was 8.3 months and overall survival was 16.2 months for those participating in the dose-escalation trial.
• Copiktra had an acceptable safety profile among patients with relapsed or refractory PTCL, which was consistent with findings from previous trials.

The safety and efficacy of Copiktra in patients with confirmed relapsed or refractory PTCL is currently being assessed in the ongoing PRIMO Phase 2 trial (NCT03372057).

“Patients with relapsed or refractory PTCL who were treated with duvelisib demonstrated preliminary, but compelling clinical activity,” Steven Horwitz, MD, Memorial Sloan Kettering Cancer Center, co-principal investigator of the Phase 1 and 2 studies, and presenter of the findings at ICML, said in a press release.

“Although the patient numbers are small in these two Phase 1 studies, we see a positive trend in response rates. The goal of the ongoing Phase 2 PRIMO study is to provide guidance on a duvelisib monotherapy dosing regimen in patients with relapsed or refractory PTCL and to further characterize its efficacy and tolerability in this population,” Horwitz added.