A supplemental new drug application has been submitted to the FDA seeking approval for the combination of copanlisib and rituximab for the treatment of relapsed indolent B-cell non-Hodgkin’s Lymphoma and is outside of the FDA accelerated approved indication for the treatment of relapsed follicular lymphoma who have received at least 2 prior systemic therapies.
A supplemental new drug application has been submitted to the FDA seeking approval for the combination of copanlisib (Aliqopa) and rituximab (Rituxan) for the treatment of relapsed indolent B-cell non-Hodgkin’s Lymphoma (iNHL) and is outside of the FDA accelerated approved indication for the treatment of relapsed follicular lymphoma who have received at least 2 prior systemic therapies, according to a press release by Bayer AG.
Copanlisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor with activity predominantly directed against PI3K-α and PI3K-δ, was granted an accelerated approval in 2017. The agent produces tumor cell death through the inhibition of proliferation of primary malignant b cell lines and apoptosis. Additionally, the agent inhibitors B-cell receptor signaling, CXCR12 mediated chemotaxis of malignant b cells, and NFkB signaling in lymphoma cells.
Bayer is also submitted the combination for a marketing authorization application from the European Medicines Agency.
The submission is supported by data from the phase 3 CHRONOS-3 (NCT02367040) study. The randomized, double-blind, placebo-controlled study has an actual enrollment of 458 participants and an estimated competition date of January 2023. The primary end point of the study is progression-free survival (PFS) up to 59 months. Secondary end points of the study include objective tumor response, duration of response, complete response, time to progression, overall survival (OS), number of participants with adverse events (AEs) as a measure of safety and tolerability, time to deterioration in DRS-P of at least 3 points as measured by the FLymSI-18 Lymphoma Symptom Index, and the time to improvement in DRS-P of at least 3 points as measured by the same index.
During the study, patients were randomized into 1 of 2 arms. In the experimental arm, 307 patients received a combination of copanlisib and rituximab. In the control arm, 151 patients received a placebo plus rituximab.
At the median follow-up of 19.2 months, the PFS for the experiment group was 21.5 months (95% CI 17.8–33.0) and 13.8 months for the control group (10.2–17.5; hazard ratio 0.52 [95% CI 0.39–0.69]; P < .0001).2
Grade 3-4 hyperglycemia occurred in 56% of patients in the experimental group and 8% of patients in the control group. It was the most common AE reported in the experimental group. Additionally, grade 3-4 hypertension occurred in 40% of patients in the experimental arm and 9% of patients in the control arm. Serious treatment-emergent AEs were also more common in the experiment group, occurring at a rate of 47% versus 18%. One drug-related death caused by pneumonitis occurred in the combination group and none were reported in the control group.
“The [United States] and EU submissions of the novel combination of Aliqopa and rituximab bring us forward in advancing new treatment approaches and addressing unmet needs of patients with different types of relapsed iNHL,” said Scott Z. Fields, MD, senior vice president and head of oncology development at Bayer in a press release. “We are excited about the potential of this investigational combination therapy based on the findings from CHRONOS-3 and we look forward to working with global regulatory authorities.”
In order to participate, patients be 18 years of age or older, have a confirmed diagnosis of non-Hodgkin lymphoma, have relapsed disease after last rituximab, rituximab biosimilar, or anti-CD20 monoclonal antibody therapy, have at least one bi-dimensionally measurable lesion, an EGOC score of 2 or less, and a life expectancy of at least 3 months. Patients with a diagnosis of chronic lymphocytic leukemia, a treatment free interval of less than 12 months since last rituximab, rituximab biosimilar, or anti-CD20 monoclonal antibody therapy, a history of interstitial lung disease, or known lymphomatous involvement of the central nervous system are not eligible to participate.