Bayer Submits NMPA Application for Copanlisib in Combination with Rituximab for Second-Line Treatment of Indolent Non-Hodgkin Lymphoma

On July 8, 2021, Bayer announced that the marketing authorization application for the innovative combination therapy of copanlisib and rituximab has been accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA). Previously, in March 2021, Bayer had submitted a marketing authorization application to the CDE for copanlisib as a monotherapy for the treatment of relapsed or refractory follicular lymphoma (FL), which was accepted by the CDE and granted priority review status. The registration application submitted this time for the combination therapy of copanlisib and rituximab is indicated for the second-line treatment of indolent non-Hodgkin lymphoma (i-NHL).

This application is supported by the positive results from the Phase III CHRONOS-3 trial, which were presented at the American Association for Cancer Research (AACR) Annual Meeting held in April 2021 and concurrently published in *The Lancet Oncology*.

Non-Hodgkin lymphoma (NHL) is the most common hematologic malignancy and the tenth most common cancer globally, with nearly 510,000 newly diagnosed cases in 2018. Each year, NHL causes nearly 250,000 deaths worldwide. Indolent NHL comprises multiple subtypes, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). Although the disease typically grows slowly, it can become more aggressive over time. Despite advances in treatment, there remains a need to improve therapeutic options for the relapsed or refractory setting. Following an initial response to therapy, response rates to subsequent-line treatments decline and the duration of response shortens, underscoring the unmet treatment needs for patients with disease progression. Registration submission data based on the results of the Phase III CHRONOS-3 trial demonstrate that copanlisib in combination with rituximab significantly improves the primary endpoint of progression-free survival in patients with relapsed iNHL.

About the CHRONOS-3 Study

The CHRONOS-3 study is a Phase III, randomized, double-blind, placebo-controlled trial designed to evaluate whether copanlisib in combination with rituximab is superior to placebo plus rituximab in prolonging progression-free survival (PFS) in patients with relapsed iNHL who have received at least one prior rituximab-containing regimen. The study enrolled patients who had no disease progression following their most recent rituximab-containing regimen, had a treatment-free interval of ≥12 months after completion of their last therapy, or were unwilling or unfit for chemotherapy, or for whom chemotherapy was contraindicated due to age, comorbidities, and/or residual toxicity.

Data from CHRONOS-3 demonstrated that intravenous copanlisib in combination with rituximab significantly improved the primary endpoint of progression-free survival (PFS) compared with rituximab plus placebo. The adverse event (AE) profile of the combination therapy was generally consistent with previously published data for the individual agents, with no new safety signals identified.

About Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) is a highly heterogeneous chronic disease with a poor prognosis. NHL is the most common hematologic malignancy and the tenth most common cancer globally, with nearly 510,000 newly diagnosed cases in 2018. Each year, NHL causes nearly 250,000 deaths worldwide.

Indolent NHL encompasses multiple subtypes, including follicular lymphoma (FL), marginal zone lymphoma (MZL), small lymphocytic lymphoma (SLL), and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM). Although the disease typically progresses slowly, it can become more aggressive over time. Despite advances in treatment, there remains a critical need to improve therapeutic options for the relapsed or refractory setting. Following an initial response, response rates decline and the duration of response shortens with subsequent lines of therapy, underscoring the unmet medical need for patients experiencing disease progression.

About Copanlisib (Aliqopa™)

Developed by Bayer, copanlisib is a pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor that exhibits inhibitory activity against the four PI3K isoforms expressed in malignant B cells, including the PI3K-α and PI3K-δ subtypes. Copanlisib is also the only PI3K inhibitor administered via intermittent intravenous infusion, which effectively inhibits the PI3K pathway in tumor cells while limiting toxicity to healthy cells. The PI3K pathway is involved in cellular growth, survival, and metabolism, and its aberrant activation occurs across various solid tumor and hematologic malignancy types, including all subtypes of iNHL. Its dysregulation plays an important role in the development of lymphoma.

Copanlisib is currently approved in the United States and Israel, among other regions, under the trade name Aliqopa™, for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior systemic therapies. The approval was based on the results of the open-label, single-arm Phase II CHRONOS-1 study (NCT01660451), which enrolled 104 adult patients with relapsed follicular B-cell non-Hodgkin lymphoma (NHL) following at least two prior systemic therapies. All patients received copanlisib monotherapy, achieving an overall response rate (ORR) of 59%, including a 14% complete response (CR) rate. Updated data from the CHRONOS-1 study published in the *American Journal of Hematology* in 2020 showed an ORR of 59% in patients with follicular B-cell NHL, including a 20% CR rate. In China, the marketing application for this indication has been granted priority review. Based on clinical data from patients with marginal zone lymphoma (MZL) enrolled in the CHRONOS-1 study, copanlisib has also received Breakthrough Therapy Designation for MZL in both the United States and China.

Bayer plans to submit regulatory applications globally based on data from CHRONOS-3.

The clinical development program for copanlisib also includes the CHRONOS-4 Phase III study, evaluating copanlisib in combination with standard immunochemotherapy for the treatment of relapsed iNHL.

Responsible Editor: Liu Li

Disclaimer: This article is reposted by Yaozhi.com. The copyright belongs to the original author. It is published for the purpose of disseminating information and does not represent the views of this platform. Should you have any concerns regarding the content, copyright, or other issues, please contact us via the website's message board, and we will promptly remove the content!