Two Phase 3 trials will assess the potential of Bayer’s copanlisib in combination with other treatment in patients with relapsed indolent B-cell non-Hodgkin’s lymphoma, based on positive data from a Phase 2 trial of the drug as a single treatment.
Researchers from Memorial Sloan-Kettering Cancer Center in New York presented the studies at the Sept. 8-12 European Society for Medical Oncology (ESMO) 2017 Congress in Madrid, Spain.
Their presentation was titled, “Phase III randomized, double-blind, controlled studies of the PI3K inhibitor copanlisib in combination with rituximab or rituximab-based chemotherapy in subjects with relapsed indolent B-cell non-Hodgkin’s lymphoma (iNHL): CHRONOS-3 and CHRONOS-4.”
While the Phase 2 CHRONOS-1 study (NCT01660451) made clear that copanlisib monotherapy is a valuable therapeutic option for patients with indolent non-Hodgkin’s lymphoma — prompting Bayer to seek accelerated approval for the drug — the company believes that even better results might be obtained when copanlisib is combined with other treatments.
The two trials include patients with indolent non-Hodgkin’s lymphoma of various types: follicular lymphoma; marginal zone lymphoma; small lymphocytic lymphoma; and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia.
Included patients had relapsed but were not refractory to treatment after at least one course of Rituxan-based therapy. Researchers will assess progression-free survival as the main outcome in the two trials.
The CHRONOS-3 study will give patients copanlisib plus Rituxan (rituximab). The study includes 567 patients who are either unfit or unwilling to have chemotherapy, or have progressed or relapsed within 12 months after the last Rituxan-based treatment.
For every two patients receiving the copanlisib combination, one will receive a placebo infusion with Rituxan.
CHRONOS-4 differs in a number of aspects. First, it will evaluate copanlisib in combination with either Rituxan plus bendamustine (R-B) or Rituxan in combination with cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone (R-CHOP). These combinations will be compared to R-B or R-CHOP with a placebo.
The study started with a run-in phase in which patients received 45 mg and 60 mg copanlisib with R-B or R-CHOP while researchers kept an eye on the safety of the combination. A Data Monitoring Committee assessed the safety run-in phase and judged that 60 mg was an appropriate dose to use during the remainder of the trial.
Once the first safety check is over, 520 eligible patients will be randomly assigned to receive R-B or R-CHOP with either copanlisib or a placebo. After six cycles of the combinations, patients will continue treatment with copanlisib or placebo monotherapy.
Copanlisib is a compound that blocks the PI3K (phosphatidylinositol 3-kinase) enzyme. Phase 2 data showed that 59 percent of indolent lymphoma patients responded to the treatment. Twelve percent of them had a complete response, and Bayer reported that the treatment triggered responses lasting for a median of 98 weeks, or nearly two years.
The U.S. Food and Drug Administration granted the therapy priority review for the treatment of refractory or relapsed follicular lymphoma patients who have had at least two prior therapies.