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Trade names | Aliqopa |
Other names | BAY 80-6946 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a617044 |
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Routes of administration | Intravenous |
Drug class | PI3-Kinase inhibitor |
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Pharmacokinetic data | |
Protein binding | 84.2% [1] |
Metabolism | CYP3A4/5 (≈90%), CYP1A1 (≈10%) [1] |
Elimination half-life | 39.1 hours (range: 14.6 to 82.4) [1] |
Excretion | Feces (64%), Urine (22%); 14% were not recovered [1] |
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Chemical and physical data | |
Formula | C23H28N8O4 |
Molar mass | 480.529 g·mol−1 |
3D model (JSmol) | |
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Copanlisib, sold under the brand name Aliqopa, [1] is a medication used for the treatment of adults experiencing relapsed follicular lymphoma who have received at least two prior systemic therapies. [1] [2]
Data for safety and efficacy of copanlisib are described in the consumer-targeted FDA Drug Trial Snapshot. [3] 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 can cause harm to unborn babies.
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. [1]
Efficacy resulting in the approval of copanlisib was based on the subgroup of 104 patients with follicular lymphoma from a Phase 2 clinical trial. [4] Of these, 59 percent had a complete or partial shrinkage of their tumors that lasted about 12 months.
To assess the safety of the drug, data from 168 adults with follicular lymphoma and other hematologic malignancies treated with copanlisib were evaluated. [3]
Phase II clinical trials are in progress for treatment of endometrial cancer, [5] diffuse large B-cell lymphoma, [6] cholangiocarcinoma, [7] and non-Hodgkin lymphoma. [4] 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). [8] Two separate phase III trials are investigating the use of copanlisib in combination with rituximab for indolent NHL [9] and the other using copanlisib alone in cases of rituximab-refractory indolent NHL. [10]
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. [11] Consequently, treatments of copanlisib with trastuzumab are being clinically trialled in HER2-positive breast cancer patients. [12]
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. [13] The New drug application for follicular lymphoma was granted priority review in May 2017. [14]
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. [15]
Copanlisib was granted orphan drug status for the treatment of splenic, nodal and extranodal subtypes of marginal zone lymphoma. [14]
Ibritumomab tiuxetan, sold under the trade name Zevalin, is a monoclonal antibody radioimmunotherapy treatment for non-Hodgkin's lymphoma. The drug uses the monoclonal mouse IgG1 antibody ibritumomab in conjunction with the chelator tiuxetan, to which a radioactive isotope is added. Tiuxetan is a modified version of DTPA whose carbon backbone contains an isothiocyanatobenzyl and a methyl group.
Targeted therapy or molecularly targeted therapy is one of the major modalities of medical treatment (pharmacotherapy) for cancer, others being hormonal therapy and cytotoxic chemotherapy. As a form of molecular medicine, targeted therapy blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with all rapidly dividing cells. Because most agents for targeted therapy are biopharmaceuticals, the term biologic therapy is sometimes synonymous with targeted therapy when used in the context of cancer therapy. However, the modalities can be combined; antibody-drug conjugates combine biologic and cytotoxic mechanisms into one targeted therapy.
Lapatinib (INN), used in the form of lapatinib ditosylate (USAN) is an orally active drug for breast cancer and other solid tumours. It is a dual tyrosine kinase inhibitor which interrupts the HER2/neu and epidermal growth factor receptor (EGFR) pathways. It is used in combination therapy for HER2-positive breast cancer. It is used for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 (ErbB2).
Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.
Pixantrone is an experimental antineoplastic (anti-cancer) drug, an analogue of mitoxantrone with fewer toxic effects on cardiac tissue. It acts as a topoisomerase II poison and intercalating agent. The code name BBR 2778 refers to pixantrone dimaleate, the actual substance commonly used in clinical trials.
Mantle cell lymphoma (MCL) is a type of non-Hodgkin's lymphoma, comprising about 6% of cases. It is named for the mantle zone of the lymph nodes where it develops. The term 'mantle cell lymphoma' was first adopted by Raffeld and Jaffe in 1991.
Chemoimmunotherapy is chemotherapy combined with immunotherapy. Chemotherapy uses different drugs to kill or slow the growth of cancer cells; immunotherapy uses treatments to stimulate or restore the ability of the immune system to fight cancer. A common chemoimmunotherapy regimen is CHOP combined with rituximab (CHOP-R) for B-cell non-Hodgkin lymphomas.
Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkin's lymphoma. It is given by injection into a vein.
Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL. The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.
Phosphoinositide 3-kinase inhibitors are a class of medical drugs that are mainly used to treat advanced cancers. They function by inhibiting one or more of the phosphoinositide 3-kinase (PI3K) enzymes, which are part of the PI3K/AKT/mTOR pathway. This signal pathway regulates cellular functions such as growth and survival. It is strictly regulated in healthy cells, but is always active in many cancer cells, allowing the cancer cells to better survive and multiply. PI3K inhibitors block the PI3K/AKT/mTOR pathway and thus slow down cancer growth. They are examples of a targeted therapy. While PI3K inhibitors are an effective treatment, they can have very severe side effects and are therefore only used if other treatments have failed or are not suitable.
Tower Cancer Research Foundation (TCRF) is a 501(c)(3) non-profit organization dedicated to clinical research, patient support and community education. It was established in 1996 in Beverly Hills, California.
Trastuzumab emtansine, sold under the brand name Kadcyla, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the cytotoxic agent DM1. Trastuzumab alone stops growth of cancer cells by binding to the HER2 receptor, whereas trastuzumab emtansine undergoes receptor-mediated internalization into cells, is catabolized in lysosomes where DM1-containing catabolites are released and subsequently bind tubulin to cause mitotic arrest and cell death. Trastuzumab binding to HER2 prevents homodimerization or heterodimerization (HER2/HER3) of the receptor, ultimately inhibiting the activation of MAPK and PI3K/AKT cellular signalling pathways. Because the monoclonal antibody targets HER2, and HER2 is only over-expressed in cancer cells, the conjugate delivers the cytotoxic agent DM1 specifically to tumor cells. The conjugate is abbreviated T-DM1.
Idelalisib, sold under the brand name Zydelig, is a medication used to treat certain blood cancers.
Polatuzumab vedotin, sold under the brand name Polivy, is a CD79b-directed antibody-drug conjugate medication used for the treatment of diffuse large B-cell lymphoma (cancer). It was developed by the Genentech subsidiary of Roche.
Duvelisib, sold under the brand name Copiktra, is a medication used to treat chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and follicular lymphoma after other treatments have failed. It is taken by mouth. It is a PI3 kinase inhibitor.
Abemaciclib, sold under the brand name Verzenio among others, is a medication for the treatment of advanced or metastatic breast cancers. It was developed by Eli Lilly and it acts as a CDK inhibitor selective for CDK4 and CDK6.
Umbralisib, sold under the brand name Ukoniq, is an anti-cancer medication for the treatment of marginal zone lymphoma (MZL) and follicular lymphoma (FL). It is taken by mouth.
Lisocabtagene maraleucel, sold under the brand name Breyanzi, is a cell-based gene therapy used to treat large B-cell lymphoma.
Selinexor sold under the brand name Xpovio among others, is a selective inhibitor of nuclear export used as an anti-cancer medication. It works by blocking the action of exportin 1 and thus blocking the transport of several proteins involved in cancer-cell growth from the cell nucleus to the cytoplasm, which ultimately arrests the cell cycle and leads to apoptosis. It is the first drug with this mechanism of action.
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