Bayer's PI3K Inhibitor Aliqopa (Copanlisib) Combined with Rituximab Achieves Positive Phase 3 CHRONOS-3 Trial Results in Relapsed Indolent Non-Hodgkin Lymphoma

October 14, 2020 /Bio ValleyBIOON/ --Bayer(Bayer) recently announced that the Phase 3 clinical study CHRONOS-3, evaluating the targeted anticancer drug Aliqopa (copanlisib) in combination with rituximab for the treatment of patients with relapsed indolent non-Hodgkin lymphoma (iNHL), met its primary endpoint of significantly prolonging progression-free survival (PFS).

CHRONOS-3 was a randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of Aliqopa plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL). A total of 458 patients were enrolled and randomized in a 2:1 ratio to receive treatment. Histological subtypes included follicular lymphoma (FL), small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), and marginal zone lymphoma (MZL).

The results showed that the study met its primary endpoint: progression-free survival (PFS) was significantly prolonged in the Aliqopa plus rituximab treatment group compared with the placebo plus rituximab group. The safety and tolerability observed in the study were generally consistent with previously published data on the individual components of the combination regimen, and no new safety signals were identified.

The results of the CHRONOS-3 study will be presented at upcoming scientific conferences. Bayer plans to discuss the CHRONOS-3 data with regulatory authorities worldwide. Bayer’s Senior Vice President andTumorDr. Scott Z. Fields, Head of Development, stated: “Indolent Non-Hodgkin Lymphoma (iNHL) is a heterogeneous group of malignantTumor, characterized by chronic remission and relapse. For patients with indolent non-Hodgkin lymphoma (iNHL) whose disease has progressed and requires treatment, there are few approved therapeutic options. The positive results from the CHRONOS-3 study confirm the clinical benefit potential of Aliqopa in combination with rituximab, addressing the unmet medical needs in these patients.”

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the tenth most common cancer type, comprising a highly heterogeneous group of diseases, classified according toTumorBased on cell proliferation rates and clinical characteristics, non-Hodgkin lymphoma (NHL) can be classified into aggressive NHL (aNHL) and indolent NHL (iNHL). iNHL includes various subtypes such as follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). Although this disease typically progresses slowly, it tends to become more aggressive over time. Despite advances in treatment, there is still a need for improved therapeutic regimens for relapsed or refractory disease. Following response to initial therapy, both response rates and duration of response decline with subsequent lines of treatment, highlighting the unmet medical needs in patients with progressive disease.

The active pharmaceutical ingredient of Aliqopa is copanlisib, a novel intravenous pan-Class I phosphatidylinositol 3-kinase (PI3K) inhibitor that primarily inhibits the PI3K-α and PI3K-δ isoforms expressed in malignant B cells. The PI3K signaling pathway is involved in cell growth, survival, and metabolism, and its dysregulation plays a significant role in non-Hodgkin lymphoma (NHL). Copanlisib has been demonstrated to induce apoptosis and inhibit proliferation in primary malignant B-cell lines.TumorCell Death. Copanlisib can inhibit several key cellular signaling pathways, including B-cell receptor signaling, CXCR12-mediated chemotaxis of malignant B cells, and NFκB signaling in lymphoma cell lines.

In the United States, Aliqopa received accelerated approval in September 2017 for adult patients with relapsed follicular lymphoma (FL) who had previously received at least two systemic therapies. Data from the open-label, single-arm Phase II CHRONOS-1 study demonstrated that monotherapy with Aliqopa achieved an overall response rate (ORR) of 59% and a complete response rate (CR) of 14% in patients with follicular B-cell non-Hodgkin lymphoma (NHL) who had previously received at least two systemic therapies. Updated data from the CHRONOS-1 study, published in the American Journal of Hematology in 2020, showed an ORR of 59% and a CR of 20% in the FL patient subgroup.

Currently, Bayer is conducting an extensive clinical development program to evaluate copanlisib in patients with relapsed or refractory indolent non-Hodgkin lymphoma (iNHL) who have previously received one or more therapies. Among these, the Phase III CHRONOS-3 study is evaluating copanlisib in combination with rituximab for the treatment of patients with relapsed iNHL, and the Phase III CHRONOS-4 study is evaluating copanlisib in combination with standard immunochemotherapy for the treatment of patients with relapsed iNHL. (Bioon.com)

Original Source: Combination of Copanlisib and Rituximab Significantly Prolonged Progression-Free Survival in Patients with Relapsed Indolent Non-Hodgkin’s Lymphoma