Bayer will present long-term safety and efficacy data from the CHRONOS-1 trial of Aliqopa (copanlisib) in patients with indolent lymphomas at the American Society of Hematology (ASH) 2017 Annual Meeting and Exposition in December.
The company has to date registered four abstracts of papers on Aliqopa as a treatment of indolent, or slow-growing, lymphomas to be presented at the Atlanta meeting.
The abstract titled “Updated Safety and Efficacy from the Copanlisib CHRONOS-1 Trial in Patients with Relapsed or Refractory Indolent B-Cell Lymphoma: Low Incidence of Late-Onset Severe Toxicities” summarizes efficacy analyses done on data collected until Feb. 20, 2017. The initial data analysis cutoff in the CHRONOS-1 Phase 2 clinical trial (NCT01660451) of Aliqopa in treating relapsed or refractory indolent B-cell lymphoma was of June 22, 2016.
Data from 142 patients were analyzed, 141 of whom had indolent lymphoma. A total of 46 patients were still receiving treatment at the 2016 cutoff. Of them, 25 were still being treated in February. There were 20 complete responses among the 83 (58.5%) tumor responses observed. Progression-free survival ranged from 0.03 to 30 months, with a mid-range of 11.3 months.
“Updated analyses based on a data cut-off of Feb 2017 reaffirmed the robust efficacy (ORR of 58.5% and median DOR >1 year [duration of response]) of copanlisib treatment in patients with relapsed or refractory indolent B-cell lymphoma,” the researchers wrote.
The abstract “Pooled Safety Analysis from Phase I and II Studies for Patients with Relapsed Indolent Non-Hodgkin’s Lymphoma Treated with Intravenous Copanlisib” outlines the safety results of a weekly intravenous (IV) administration of Aliqopa on a four-week cycle (three weeks on and one week off), instead of daily oral doses of similar treatments, in patients with relapsed indolent non-Hodgkin’s lymphoma (iNHL).
Researchers report a very different safety profile with the IV treatment regimen compared to continuous oral dosing that reports such extended-use effects as late-onset severe diarrhea leading to colitis.
Pooled data from 168 iNHL patients showed that the average duration of Aliqopa treatment was 30 weeks and “Per cycle, discontinuations due to AEs were low and evenly distributed over the entire course of treatment (2-3% per patients at risk per cycle),” the researchers wrote. Adverse events (AEs) did include 94 (56%) severe AEs and 42 (25%) Grade 4 AEs, which are life-threatening. “The highest G3/G4 events were principally hyperglycemia (32%/6%) and hypertension (27%/0%). These infusion-related events were asymptomatic, transient and largely self-limiting,” the study states.
Dose modifications were made in 115 (69%) patients and, in total, AEs led to 41 patients (24%) discontinuing treatment.
The most common AEs included high blood sugar, diarrhea, hypertension, fatigue, nausea, and low counts of a type of white blood cell.
“Efficacy of Copanlisib Monotherapy in Patients with Relapsed or Refractory Marginal Zone Lymphoma: Subset Analysis from the CHRONOS-1 Trial” will discuss results seen in 23 patients with marginal zone lymphoma (MZL) enrolled in the CHRONOS-1 trial.
Overall, 70 percent of these patients responded to the treatment, including 13 percent complete responses, with tumor shrinkage over time indicating a rapid and prolonged response. The median duration of response could not yet be measured, but 85 percent of the patients were still in response at nine months. This is “higher than what has been previously reported in the MZL treatment landscape, warranting further study of copanlisib in MZL,” the authors concluded.
Aliqopa was given accelerated approval to treat adults whose follicular lymphoma relapsed after at least two prior systemic therapies by the U.S. Food and Drug Administration in September.
The CHRONOS-3 Phase 3 study (NCT02367040) is currently evaluating Aliqopa in combination with Rituxan (rituximab) in relapsed iNHL patients. The CHRONOS-4 Phase 3 study (NCT02626455) is evaluating Aliqopa in combination with standard immunochemotherapy in relapsed iNHL. Both these clinical trials are still recruiting patients; more information is available by clicking on their respective trial identification numbers.
