Copanlisib

Data for safety and efficacy of copanlisib are described in the consumer-targeted FDA Drug Trial Snapshot. Copanlisib can cause serious side effects including infections, hyperglycemia, hypertension, pneumonitis, neutropenia and skin rashes. The most common side effects of copanlisib are hyperglycemia, diarrhea, decreased general strength and energy, hypertension, leukopenia, neutropenia, nausea, lower respiratory tract infections and thrombocytopenia.

Copanlisib is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and PI3K-δ isoforms expressed in malignant B-cells. It has been shown to induce tumor cell death by apoptosis and inhibition of proliferation of primary malignant B cell lines.

Efficacy resulting in the approval of copanlisib was based on the subgroup of 104 patients with follicular lymphoma from a phase II clinical trial.

To assess the safety of the drug, data from 168 adults with follicular lymphoma and other hematologic malignancies treated with copanlisib were evaluated.{{cite web|url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-aliqopa|archive-url=https://web.archive.org/web/20190612184736/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-aliqopa|url-status=dead|archive-date=12 June 2019|title=Drug Trials Snapshots Aliqopa|date=30 June 2020 |publisher=U.S. Food and Drug Administration (FDA) }}

Phase II clinical trials are in progress for treatment of endometrial cancer,{{ClinicalTrialsGov|NCT02728258|Copanlisib in Treating Patients With Persistent or Recurrent Endometrial Cancer}} diffuse large B-cell lymphoma,{{ClinicalTrialsGov|NCT02391116|Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)}} cholangiocarcinoma,{{ClinicalTrialsGov|NCT02631590|Copanlisib (BAY 80-6946) in Combination With Gemcitabine and Cisplatin in Advanced Cholangiocarcinoma}} and non-Hodgkin lymphoma.{{ClinicalTrialsGov|NCT01660451|Open-label, Uncontrolled Phase II Trial of Intravenous PI3K Inhibitor BAY80-6946 in Patients With Relapsed, Indolent or Aggressive Non-Hodgkin's Lymphomas}} Copanlisib in combination with R-CHOP or R-B (rituximab and bendamustine) is in a phase III trial for relapsed indolent non-Hodgkin lymphoma (NHL).{{ClinicalTrialsGov|NCT02626455|Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)}} Two separate phase III trials are investigating the use of copanlisib in combination with rituximab for indolent NHL{{ClinicalTrialsGov|NCT02367040|Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL)}} and the other using copanlisib alone in cases of rituximab-refractory indolent NHL.{{ClinicalTrialsGov|NCT02369016|Phase III Copanlisib in Rituximab-refractory iNHL}}

In a preclinical study, copanlisib was effective in inhibiting HER2+ breast cancer cells with acquired resistance to the HER2-inhibitors trastuzumab and/or lapatinib. This effect was increased when copanlisib was administered along with the aforementioned HER2-inhibitors.{{cite journal | vauthors = Elster N, Cremona M, Morgan C, Toomey S, Carr A, O'Grady A, Hennessy BT, Eustace AJ | s2cid = 25568678 | title = A preclinical evaluation of the PI3K alpha/delta dominant inhibitor BAY 80-6946 in HER2-positive breast cancer models with acquired resistance to the HER2-targeted therapies trastuzumab and lapatinib | journal = Breast Cancer Research and Treatment | volume = 149 | issue = 2 | pages = 373–83 | date = January 2015 | pmid = 25528022 | doi = 10.1007/s10549-014-3239-5 | url = https://figshare.com/articles/journal_contribution/A_preclinical_evaluation_of_the_PI3K_alpha_delta_dominant_inhibitor_BAY_80-6946_in_HER2-positive_breast_cancer_models_with_acquired_resistance_to_the_HER2-targeted_therapies_trastuzumab_and_lapatinib_/10787282/2/files/19300052.pdf }} Consequently, treatments of copanlisib with trastuzumab are being clinically trialled in HER2-positive breast cancer patients.{{ClinicalTrialsGov|NCT02705859|Phase Ib/II Trial of coPANlisib in Combination With Trastuzumab in HER2-positive Breast Cancer. (Panther Study)}}

For follicular lymphoma, the U.S. Food and Drug Administration (FDA) awarded copanlisib orphan drug designation in February 2015, and fast track designation in February 2016.{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf|archive-url=https://web.archive.org/web/20211102135809/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000MultidisciplineR.pdf|url-status=dead|archive-date=2 November 2021|title=NDA 209936, Multisciplinary Review document, chapter 3|publisher=U.S. Food and Drug Administration (FDA) }} The New drug application for follicular lymphoma was granted priority review in May 2017.

In September 2017, it received accelerated approval for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies. Further clinical trials are to be performed as a post-marketing requirement to verify the clinical benefit.{{cite web|url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/209936Orig1s000Approv.pdf|title=NDA 209936, Approval Letter|publisher=U.S. Food and Drug Administration (FDA) }}

Copanlisib was granted orphan drug status for the treatment of splenic, nodal and extranodal subtypes of marginal zone lymphoma.{{cite press release|url=https://www.bayer.com/media/bayer-receives-fda-approval-for-copanlisib-in-adults-with-relapsed-follicular-lymphoma-after-two-prior-systemic-therapies/ |title=Bayer receives FDA approval for Copanlisib in adults with relapsed follicular lymphoma after two prior systemic therapies |publisher=Bayer |date=14 September 2017}}

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Category:Antineoplastic drugs

Category:Phosphoinositide 3-kinase inhibitors

Category:4-Morpholinyl compounds

Category:Drugs developed by Bayer

Category:Orphan drugs

Category:Pyrimidines

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