COPIKTRA in patients with high-risk and heavily pretreated CLL/SLL

DUO trial: a pivotal phase 3, randomized, active-controlled, multicenter, open-label superiority trial
that met its primary endpoint of progression-free survival (PFS)3

  • Efficacy was based on a subset analysis of patients with at least 2 prior lines of therapy, where the risk:benefit ratio appeared greater in this more heavily pretreated population (n=196)1
  • Safety was based on the comprehensive overall study population (N=319)1

Key baseline characteristics (N=319)3:

  • Median age of 69 years
  • ECOG performance status of 0-2

Primary endpoint1:

  • PFS (IRC assessed)

Other efficacy measures endpoints3:

  • Overall response rate (ORR)
  • Lymph node response rate (LNRR)
  • Duration of response (DOR)

Patients in the DUO subpopulation were heavily pretreated and relapsed/refractory (n=196)1.

  • Prior types of therapies included purine analogs (74%), alkylating agents (96%), and monoclonal antibodies (87%)3
  • The median time since most recent relapse was 2.55 months before entry into DUO3

Clinically high-risk features at baseline were balanced across both treatment arms (n=196)3

Select a patient characteristic below to reveal the subpopulation percentage.

17p deletion
TP53 mutation
Rai Stage III and IV
Bulky disease
Unmutated IGHV
17p deletion
TP53 mutation
Rai Stage III and IV
Bulky disease
Unmutated IGHV

COPIKTRA demonstrated >7-month median PFS advantage vs ofatumumab (n=196)1*

Efficacy data are based on patients who received ≥2 prior therapies.

  • COPIKTRA met its primary endpoint of PFS in the DUO subpopulation3
  • There was a 62% chance of being event-free at 1 year with COPIKTRA (95% CI: 0.51-0.72) vs 34% with ofatumumab (95% CI: 0.23-0.44)3

PFS analysis was conducted for COPIKTRA vs ofatumumab across patient subgroups (n=196)3

Efficacy data are based on patients who received ≥2 prior therapies.

Study features and limitations:

  • This analysis was not powered to show statistical significance in PFS across these prespecified subgroups

  • *Kaplan-Meier estimate
  • CI, confidence interval; CLL, chronic lymphocytic leukemia; HR, hazard ratio; ITT, intention to treat; SE, standard error; SLL, small lymphocytic lymphoma.

Overall response rate: the majority of heavily pretreated patients achieved a partial response with COPIKTRA (n=196)1,3*

Efficacy data are based on patients who received ≥2 prior therapies.
  • All responses were partial responses; no patient achieved a complete response1
  • Data were evaluated based on the International Workshop on CLL or revised International Working Group response criteria, with modification for treatment-related lymphocytosis1

Additional Data

Lymph node reduction: patients experienced lymph node responses with COPIKTRA (n=196)3†

Data are based on patients who received ≥2 prior therapies.

Study features and limitations:

  • LNRR was not ranked or formally tested in the hierarchy of key secondary endpoints3
  • *

    The International Workshop on CLL or revised International Working Group response criteria, with modification for treatment-related lymphocytosis.

  • Lymph node response was defined as ≥50% reduction in target lesion size, as determined by the IRC.

  • CI, confidence interval; CLL, chronic lymphocytic leukemia; IRC, independent review committee; ITT, intention to treat; LNRR, lymph node response rate; ORR, overall response rate.

  • *

    312 patients had CLL; 7 patients had SLL (N=319).

  • COPIKTRA was administered at 25 mg BID in 28-day treatment cycles until unacceptable toxicity or progressive disease.

  • Ofatumumab was administered at an initial dose of 300 mg IV on day 1, followed a week later by 7 weekly doses of 2000 mg IV, followed 4 weeks later by 2000 mg IV every 4 weeks for 4 doses. Patients received a total of 12 doses of ofatumumab.

  • §

    In the subanalysis of patients with ≥2 prior lines of therapy (n=95).

  • Baseline lesion ≥5 cm.

  • BID, twice daily; CLL, chronic lymphocytic leukemia; δ, delta; ECOG, Eastern Cooperative Oncology Group; γ, gamma; IGHV, immunoglobulin heavy chain variable region genes; PI3K, phosphoinositide 3-kinase; SLL, small lymphocytic lymphoma.