Phase III CHRONOS-3 study evaluating copanlisib and rituximab combination meets primary endpoint

On October 14, 2020, it was announced that the phase III CHRONOS-3 study (NCT02367040), evaluating copanlisib in combination with rituximab for relapsed indolent non-Hodgkin lymphoma (iNHL), met its primary endpoint of significantly prolonging progression-free survival (PFS).¹  

Copanlisib

Copanlisib is an intravenously-administered pan inhibitor of phosphoinositide 3-kinase. In 2017, copanlisib received accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed follicular lymphoma, a decision based on the results of the phase II CHRONOS-1 trial (NCT01660451).

CHRONOS-3²

The phase III CHRONOS-3 trial is a randomized, double-blind, placebo-controlled study investigating the safety and efficacy of copanlisib plus rituximab vs placebo plus rituximab in adult patients with relapsed iNHL. The study sought to determine whether copanlisib plus rituximab is superior to placebo plus rituximab in prolonging PFS in this setting.

Patients with follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma, and lymphoplasmacytoid lymphoma/Waldenström’s macroglobulinemia who had received ≥ 1 line of prior therapy were enrolled. Additional inclusion criteria were a treatment-free interval of ≥ 12 months following last rituximab-based treatment or ineligibility for chemotherapy. Patients (N = 458) were randomized 2:1 to receive copanlisib plus rituximab vs placebo plus rituximab in the following dosing regimens:

• Copanlisib or placebo: Days 1, 8, and 15 of each 28-day cycle
• Rituximab:
  • Weekly on Days 1, 8, 15, and 22 of Cycle 1
  • Day 1 of Cycles 3, 5, 7, and 9

Full safety and efficacy data from the CHRONOS-3 study are due to be released later this year.