DOCSLIB.ORG

209936Orig1s000

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
209936Orig1s000 CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 209936Orig1s000 MULTI-DISCIPLINE REVIEW Summary Review Office Director Cross Discipline Team Leader Review Clinical Review Non-Clinical Review Statistical Review Clinical Pharmacology Review NDA/BLA Multi-disciplinary Review and Evaluation NDA 209936 Aliqopa (copanlisib) NDA/BLA Multi-disciplinary Review and Evaluation Application Type New Drug Application (NDA) Application Number(s) 209936 Priority or Standard Priority Submit Date(s) 16 March 2017 Received Date(s) 16 March 2017 PDUFA Goal Date 16 November 2017 Division/Office DHP/OHOP Review Completion Date 13 September 2017 Established Name Copanlisib (Proposed) Trade Name Aliqopa Pharmacologic Class Kinase inhibitor Code name Phosphatidylinositol 3-kinase (PI3K) inhibitor Applicant Bayer HealthCare Pharmaceuticals Inc. Formulation(s) 60 mg intravenous infusion Dosing Regimen Days 1, 8, and 15 of a 28-day treatment cycle Applicant Proposed Indicated for the treatment of patients with relapsed (b) (4) Indication(s)/Population(s) follicular lymphoma who have received at least two prior therapies. Recommendation on Accelerated Approval Regulatory Action Recommended Indicated for the treatment of adult patients with relapsed Indication(s)/Population(s) follicular lymphoma who have received at least two prior systemic (if applicable) therapies. 1 Reference ID: 4151882 NDA/BLA Multi-disciplinary Review and Evaluation NDA 209936 Aliqopa (copanlisib) Table of Contents Reviewers of Multi-Disciplinary Review and Evaluation ................................................................ 9 Additional Reviewers of Application ............................................................................................... 9 Glossary ......................................................................................................................................... 10 1 Executive Summary ............................................................................................................... 12 1.1. Product Introduction ...................................................................................................... 12 1.2. Conclusions on the Substantial Evidence of Effectiveness ............................................ 12 1.3. Benefit-Risk Assessment ................................................................................................ 14 2 Therapeutic Context .............................................................................................................. 17 2.1. Analysis of Condition ...................................................................................................... 17 2.2. Analysis of Current Treatment Options ......................................................................... 17 3 Regulatory Background ......................................................................................................... 21 3.1. U.S. Regulatory Actions and Marketing History ............................................................. 21 3.2. Summary of Presubmission/Submission Regulatory Activity ........................................ 21 4 Significant Issues from Other Review Disciplines Pertinent to Clinical Conclusions on Efficacy and Safety................................................................................................................. 22 4.1. Office of Scientific Investigations (OSI) .......................................................................... 22 4.2. Product Quality .............................................................................................................. 22 4.3. Devices and Companion Diagnostic Issues .................................................................... 23 5 Nonclinical Pharmacology/Toxicology................................................................................... 24 5.1. Executive Summary ........................................................................................................ 24 5.2. Referenced NDAs, BLAs, DMFs ....................................................................................... 27 5.3. Pharmacology ................................................................................................................. 27 5.4. ADME/PK ........................................................................................................................ 35 5.5. Toxicology ....................................................................................................................... 37 5.5.1. General Toxicology .................................................................................................. 37 5.5.2. Genetic Toxicology .................................................................................................. 44 5.5.3. Carcinogenicity ........................................................................................................ 45 5.5.4. Reproductive and Developmental Toxicology ........................................................ 45 5.5.5. Other Toxicology Studies ........................................................................................ 49 2 Reference ID: 4151882 NDA/BLA Multi-disciplinary Review and Evaluation NDA 209936 Aliqopa (copanlisib) 6 Clinical Pharmacology ............................................................................................................ 51 6.1. Executive Summary ........................................................................................................ 51 6.2. Summary of Clinical Pharmacology Assessment ............................................................ 54 6.2.1. Pharmacology and Clinical Pharmacokinetics ........................................................ 54 6.2.2. General Dosing and Therapeutic Individualization ................................................. 55 6.3. Comprehensive Clinical Pharmacology Review ............................................................. 56 6.3.1. General Pharmacology and Pharmacokinetic Characteristics ................................ 56 6.3.2. Clinical Pharmacology Questions ............................................................................ 58 7 Statistical and Clinical Evaluation .......................................................................................... 68 7.1. Sources of Clinical Data and Review Strategy ................................................................ 68 7.1.1. Table of Clinical Studies .......................................................................................... 68 7.1.2. Review Strategy ...................................................................................................... 69 7.2. Review of Relevant Individual Trials Used to Support Efficacy ...................................... 69 7.2.1. Study 16349 Part B .................................................................................................. 69 7.2.2. Study Results ........................................................................................................... 75 7.3. Integrated Review of Effectiveness ................................................................................ 88 7.3.1. Assessment of Efficacy Across Trials ....................................................................... 88 7.3.2. Integrated Assessment of Effectiveness ................................................................. 90 7.4. Review of Safety ............................................................................................................. 90 7.4.1. Safety Review Approach ......................................................................................... 90 7.4.2. Review of the Safety Database ............................................................................... 91 7.4.3. Adequacy of Applicant’s Clinical Safety Assessments ............................................ 95 7.4.4. Safety Results .......................................................................................................... 95 7.4.5. Analysis of Submission-Specific Safety Issues ....................................................... 113 7.4.6. Safety Analyses by Demographic Subgroups ........................................................ 128 7.4.7. Specific Safety Studies/Clinical Trials .................................................................... 130 7.4.8. Additional Safety Explorations .............................................................................. 130 7.4.9. Safety in the Postmarket Setting .......................................................................... 130 7.4.10. Integrated Assessment of Safety ................................................................... 131 SUMMARY AND CONCLUSIONS .................................................................................................. 134 7.5. Statistical Issues ........................................................................................................... 134 7.6. Conclusions and Recommendations ............................................................................ 134 3 Reference ID: 4151882 NDA/BLA Multi-disciplinary Review and Evaluation NDA 209936 Aliqopa (copanlisib) 8 Advisory Committee Meeting and Other External Consultations ....................................... 136 9 Pediatrics ............................................................................................................................. 137 10 Labeling Recommendations ...............................................................................................
Load more

Recommended publications
  • PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects
    International Journal of Molecular Sciences Review PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects Rosalin Mishra , Hima Patel, Samar Alanazi , Mary Kate Kilroy and Joan T. Garrett * Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA; [email protected] (R.M.); [email protected] (H.P.); [email protected] (S.A.); [email protected] (M.K.K.) * Correspondence: [email protected]; Tel.: +1-513-558-0741; Fax: +1-513-558-4372 Abstract: The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted. Keywords: cancer; PIK3CA; resistance; PI3K inhibitors Citation: Mishra, R.; Patel, H.; Alanazi, S.; Kilroy, M.K.; Garrett, J.T.
    [Show full text]
  • DRUGS REQUIRING PRIOR AUTHORIZATION in the MEDICAL BENEFIT Page 1
    Effective Date: 08/01/2021 DRUGS REQUIRING PRIOR AUTHORIZATION IN THE MEDICAL BENEFIT Page 1 Therapeutic Category Drug Class Trade Name Generic Name HCPCS Procedure Code HCPCS Procedure Code Description Anti-infectives Antiretrovirals, HIV CABENUVA cabotegravir-rilpivirine C9077 Injection, cabotegravir and rilpivirine, 2mg/3mg Antithrombotic Agents von Willebrand Factor-Directed Antibody CABLIVI caplacizumab-yhdp C9047 Injection, caplacizumab-yhdp, 1 mg Cardiology Antilipemic EVKEEZA evinacumab-dgnb C9079 Injection, evinacumab-dgnb, 5 mg Cardiology Hemostatic Agent BERINERT c1 esterase J0597 Injection, C1 esterase inhibitor (human), Berinert, 10 units Cardiology Hemostatic Agent CINRYZE c1 esterase J0598 Injection, C1 esterase inhibitor (human), Cinryze, 10 units Cardiology Hemostatic Agent FIRAZYR icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent HAEGARDA c1 esterase J0599 Injection, C1 esterase inhibitor (human), (Haegarda), 10 units Cardiology Hemostatic Agent ICATIBANT (generic) icatibant J1744 Injection, icatibant, 1 mg Cardiology Hemostatic Agent KALBITOR ecallantide J1290 Injection, ecallantide, 1 mg Cardiology Hemostatic Agent RUCONEST c1 esterase J0596 Injection, C1 esterase inhibitor (recombinant), Ruconest, 10 units Injection, lanadelumab-flyo, 1 mg (code may be used for Medicare when drug administered under Cardiology Hemostatic Agent TAKHZYRO lanadelumab-flyo J0593 direct supervision of a physician, not for use when drug is self-administered) Cardiology Pulmonary Arterial Hypertension EPOPROSTENOL (generic)
    [Show full text]
  • R&D Briefing 76
    The Impact of Recent Regulatory Developments on the Mexican Therapeutic Landscape Access to innovative medicines is key to El acceso a medicamentos innovadores es clave para improving overall population health, reducing mejorar la salud de toda la población, para reducir los hospitalisation time and decreasing morbidity and tiempos de hospitalización, la morbilidad y la mortalidad mortality. An efficient regulatory process can be de un país. Un proceso regulatorio eficiente tiene un reflected in measurable positive health impacts; impacto positivo medible en la salud, y por el contrario, conversely, activities that slow or impede acciones que retrasan o impiden la eficiencia regulatoria y regulatory efficiency and predictability can be su predictibilidad pueden ser perjudiciales. La parálisis detrimental. Recent developments in the Mexican reciente del Sistema regulatorio mexicano respecto a la regulatory system for the assessments of evaluación de nuevos medicamentos innovadores innovative new products have had a negative conlleva un impacto negativo en la salud de la población impact on Mexican public health. mexicana. This Briefing addresses the impact of suspending Este informe analiza el impacto de la suspensión de las the activities of the New Molecules Committee actividades del Comité de Moléculas Nuevas (NMC, por (NMC) on the Mexican therapeutic landscape. sus siglas en inglés) sobre el horizonte terapéutico de First, we compared the way that “new medicines” México. En primer lugar, comparamos la definición de are defined within the context of the Mexican nuevos medicamentos según el contexto regulatorio regulatory system, with definitions used by mexicano con las definiciones adoptadas por otras comparable regulators and health organisations. agencias reguladoras u organizaciones de salud del We have also investigated the extent to which mundo.
    [Show full text]
  • New Drug Update: the Next Step in Personalized Medicine
    New Drug Update: The Next Step in Personalized Medicine Jordan Hill, PharmD, BCOP Clinical Pharmacy Specialist WVU Medicine Mary Babb Randolph Cancer Center Objectives • Review indications for new FDA approved anti- neoplastic medications in 2017 • Outline place in therapy of new medications • Become familiar with mechanisms of action of new medications • Describe adverse effects associated with new medications • Summarize dosing schemes and appropriate dose reductions for new medications First-in-Class Approvals • FLT3 inhibitor – midostaurin • IDH2 inhibitor – enasidenib • Anti-CD22 antibody drug conjugate – inotuzumab ozogamicin • CAR T-cell therapy - tisagenlecleucel “Me-too” Approvals • CDK 4/6 inhibitor – ribociclib and abemaciclib • PD-L1 inhibitors • Avelumab • Durvalumab • PARP inhibitor – niraparib • ALK inhibitor – brigatinib • Pan-HER inhibitor – neratinib • Liposome-encapsulated combination of daunorubicin and cytarabine • PI3K inhibitor – copanlisib Drugs by Malignancy AML Breast Bladder ALL FL Lung Ovarian 0 1 2 3 Oral versus IV 46% 54% Oral IV FIRST-IN CLASS FLT3 Inhibitor - midostaurin Journal of Hematology & Oncology 2017;10:93 Midostaurin (Rydapt®) • 717 newly diagnosed FLT3+ AML Patients • Induction and consolidation chemotherapy and placebo maintenance versus chemotherapy + midostaurin and Treatment maintenance midostaurin • OS: 74.7 mo versus 25.6 mo (P=0.009) Efficacy • EFS: 8.2 mo versus 3.0 mo (P=0.002) • Higher grade > 3 anemia, rash, and nausea Safety N Engl J Med 2017;377:454-64 Midostaurin (Rydapt®) • Approved indications: FLT3+ AML, mast cell leukemia, systemic mastocytosis • AML dose: 50 mg twice daily with food on days 8-21 • Of each induction cycle (+ daunorubicin and cytarabine) • Of each consolidation cycle (+ high dose cytarabine) • ADEs: nausea, myelosuppression, mucositis, increases in LFTs, amylase/lipase, and electrolyte abnormalities • Pharmacokinetics: hepatic metabolism, substrate of CYP 3A4; < 5% excretion in urine RYDAPT (midostaurin) [package insert].
    [Show full text]
  • Phase I/II Clinical Trial of Temsirolimus and Lenalidomide in Patients with Relapsed and Refractory Lymphomas by Ajay Major, Justin Kline, Theodore G
    Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas by Ajay Major, Justin Kline, Theodore G. Karrison, Paul A.S. Fishkin, Amy S. Kimball, Adam M. Petrich, Sreenivasa Nattam, Krishna Rao, Bethany G. Sleckman, Kenneth Cohen, Koen van Besien, Aaron P. Rapoport, and Sonali M. Smith Received: April 18, 2021. Accepted: July 22, 2021. Citation: Ajay Major, Justin Kline, Theodore G. Karrison, Paul A.S. Fishkin, Amy S. Kimball, Adam M. Petrich, Sreenivasa Nattam, Krishna Rao, Bethany G. Sleckman, Kenneth Cohen, Koen van Besien, Aaron P. Rapoport and Sonali M. Smith. Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas. Haematologica. 2021 Jul 29. doi: 10.3324/haematol.2021.278853. [Epub ahead of print] Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will then appear in a regular issue of the journal. All legal disclaimers that apply to the journal also pertain to this production process. Phase I/II TEM/LEN clinical trial Phase I/II clinical trial of temsirolimus and lenalidomide in patients with relapsed and refractory lymphomas Ajay Major1; Justin Kline1; Theodore G.
    [Show full text]
  • Drug Resistance in Non-Hodgkin Lymphomas
    International Journal of Molecular Sciences Review Drug Resistance in Non-Hodgkin Lymphomas Pavel Klener 1,2,* and Magdalena Klanova 1,2 1 First Department of Internale Medicine-Hematology, University General Hospital in Prague, 128 08 Prague, Czech Republic; [email protected] 2 Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, 128 53 Prague, Czech Republic * Correspondence: [email protected] or [email protected] Received: 3 February 2020; Accepted: 15 March 2020; Published: 18 March 2020 Abstract: Non-Hodgkin lymphomas (NHL) are lymphoid tumors that arise by a complex process of malignant transformation of mature lymphocytes during various stages of differentiation. The WHO classification of NHL recognizes more than 90 nosological units with peculiar pathophysiology and prognosis. Since the end of the 20th century, our increasing knowledge of the molecular biology of lymphoma subtypes led to the identification of novel druggable targets and subsequent testing and clinical approval of novel anti-lymphoma agents, which translated into significant improvement of patients’ outcome. Despite immense progress, our effort to control or even eradicate malignant lymphoma clones has been frequently hampered by the development of drug resistance with ensuing unmet medical need to cope with relapsed or treatment-refractory disease. A better understanding of the molecular mechanisms that underlie inherent or acquired drug resistance might lead to the design of more effective front-line treatment algorithms based on reliable predictive markers or personalized salvage therapy, tailored to overcome resistant clones, by targeting weak spots of lymphoma cells resistant to previous line(s) of therapy. This review focuses on the history and recent advances in our understanding of molecular mechanisms of resistance to genotoxic and targeted agents used in clinical practice for the therapy of NHL.
    [Show full text]
  • Standard Oncology Criteria C16154-A
    Prior Authorization Criteria Standard Oncology Criteria Policy Number: C16154-A CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DATE DUE BEFORE 03/2016 12/2/2020 1/26/2022 HCPCS CODING TYPE OF CRITERIA LAST P&T APPROVAL/VERSION N/A RxPA Q1 2021 20210127C16154-A PRODUCTS AFFECTED: See dosage forms DRUG CLASS: Antineoplastic ROUTE OF ADMINISTRATION: Variable per drug PLACE OF SERVICE: Retail Pharmacy, Specialty Pharmacy, Buy and Bill- please refer to specialty pharmacy list by drug AVAILABLE DOSAGE FORMS: Abraxane (paclitaxel protein-bound) Cabometyx (cabozantinib) Erwinaze (asparaginase) Actimmune (interferon gamma-1b) Calquence (acalbrutinib) Erwinia (chrysantemi) Adriamycin (doxorubicin) Campath (alemtuzumab) Ethyol (amifostine) Adrucil (fluorouracil) Camptosar (irinotecan) Etopophos (etoposide phosphate) Afinitor (everolimus) Caprelsa (vandetanib) Evomela (melphalan) Alecensa (alectinib) Casodex (bicalutamide) Fareston (toremifene) Alimta (pemetrexed disodium) Cerubidine (danorubicin) Farydak (panbinostat) Aliqopa (copanlisib) Clolar (clofarabine) Faslodex (fulvestrant) Alkeran (melphalan) Cometriq (cabozantinib) Femara (letrozole) Alunbrig (brigatinib) Copiktra (duvelisib) Firmagon (degarelix) Arimidex (anastrozole) Cosmegen (dactinomycin) Floxuridine Aromasin (exemestane) Cotellic (cobimetinib) Fludara (fludarbine) Arranon (nelarabine) Cyramza (ramucirumab) Folotyn (pralatrexate) Arzerra (ofatumumab) Cytosar-U (cytarabine) Fusilev (levoleucovorin) Asparlas (calaspargase pegol-mknl Cytoxan (cyclophosphamide)
    [Show full text]
  • Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer
    cancers Review Therapeutic Potential of PARP Inhibitors in the Treatment of Metastatic Castration-Resistant Prostate Cancer Albert Jang 1 , Oliver Sartor 1,2, Pedro C. Barata 1,2 and Channing J. Paller 3,* 1 Deming Department of Medicine, Hematology-Oncology Section, Tulane University School of Medicine, New Orleans, LA 70112, USA; [email protected] (A.J.); [email protected] (O.S.); [email protected] (P.C.B.) 2 Tulane Cancer Center, New Orleans, LA 70112, USA 3 The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA * Correspondence: [email protected]; Tel.: +1-410-955-8239; Fax: +1-410-955-8587 Received: 8 October 2020; Accepted: 19 November 2020; Published: 21 November 2020 Simple Summary: In recent years, the development of sequencing techniques to reveal the genomic information of prostate cancer tumors has allowed for the emergence of targeted therapies. Genomic aberrations in tumor cells have become popular due to the successful development of PARP inhibitors, which are particularly active in those tumors harboring DNA repair genomic defects. This review focuses on PARP inhibitors, two of which were approved for use by the US Food and Drug Administration in 2020 in metastatic castration-resistant prostate cancer. The article highlights the development of PARP inhibitors in the preclinical setting, summarizes the impactful clinical trials in the field, and discusses the need for continued research for further success in treating men with advanced prostate cancer. Abstract: Metastatic castration-resistant prostate cancer (mCRPC) is an incurable malignancy with a poor prognosis. Up to 30% of patients with mCRPC have mutations in homologous recombination repair (HRR) genes.
    [Show full text]
  • Hematology Profile Plus
    175 Technology Drive, Suite 100, Irvine, CA 92618 Tel: 1-866-484-8870 genomictestingcooperative.com CLIA #: 05D2111917 CAP #: 9441547 Hematology Profile Plus Patient Name: Ordering Physician: Date of Birth: 10/11/1960 Physician ID: Gender (M/F): M Accession #: 100712 Client: Specimen Type: Tissue Case #: Specimen ID: Body Site: Lymph node MRN: Indication for Testing: C83.90 Non-follicular (diffuse) lymphoma unspecified, unspecified site Collected Date: 02/18/2019 Time: 12:00 AM Received Date: 08/07/2019 Time: 11:50 AM Reported Date: 08/20/2019 Time: 08:13 AM Test Description: This is a comprehensive molecular profile which uses next generation sequencing (NGS), fragment length analysis and Sanger Sequencing testing to identify molecular abnormalities in DNA of 177 genes and RNA in 68 genes implicated in hematologic neoplasms, including leukemia, lymphoma melanoma and MDS. Whenever possible, clinical relevance and implications of detected abnormalities are described below. Detected Genomic Alterations Detected Genomic Alterations PRDM1 CD79B (Double) CDK12 KDM6A HUWE1 ARHGEF12 SPOP Heterogeneity Heterogeneity There is a dominant abnormal clone with PRDM1 mutation. The CD79B, CDK12, KDM6A, HUWE1, ARHGEF12, and SPOP mutations are detected in subclones. Expression Expression Expression of B-cell markers (CD19, CD22, CD79A, Significantly high expression of PD-L1 and CTLA4 PAX5). However, CD79B mRNA is relatively low. mRNA High expression of Ki67 mRNA Expression profile consistent with ABC type 1 Diagnostic Implications Diagnostic Implications
    [Show full text]
  • Optimal Management of Adverse Events from Copanlisib in the Treatment of Patients with Non-Hodgkin Lymphomas
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Clin Lymphoma Manuscript Author Myeloma Manuscript Author Leuk. Author manuscript; available in PMC 2020 March 01. Published in final edited form as: Clin Lymphoma Myeloma Leuk. 2019 March ; 19(3): 135–141. doi:10.1016/j.clml.2018.11.021. Optimal Management of Adverse Events From Copanlisib in the Treatment of Patients With Non-Hodgkin Lymphomas Bruce D. Cheson1, Susan O’Brien2, Michael S. Ewer3, Marcus D. Goncalves4, Azeez Farooki5, Georg Lenz6, Anthony Yu7, Richard I. Fisher8, Pierre L. Zinzani9, and Martin Dreyling10 1Department of Internal Medicine, Division of Hematology-Oncology, Georgetown Lombardi Comprehensive Cancer Center, Washington, DC 2Department of Medicine, University of California, Irvine, CA 3Department of Cardiology, University of Texas MD Anderson Cancer Center, Houston, TX 4Department of Endocrinology, Weill Cornell Medical Center, New York, NY 5Department of Endocrinology, Memorial Sloan Kettering Cancer Center, New York, NY 6Department of Hematology, Oncology and Pneumology, Universität Münster, Münster, Germany 7Department of Cardiology, Memorial Sloan Kettering Cancer Center, New York, NY 8Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA 9Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Bologna, Italy 10Department of Internal Medicine, University of Munich, Munich, Germany Abstract Copanlisib, an intravenously administered agent with inhibitory activity that predominantly targets the alpha and delta isoforms of phosphoinositol 3-kinase, was granted accelerated approval by the United States Food and Drug Administration on the basis of its activity in the third-line treatment of follicular non-Hodgkin lymphoma. Copanlisib is associated with several potentially serious adverse conditions, some of which are not shared with other phosphoinositol 3-kinase inhibitors This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
    [Show full text]
  • ALIQOPA Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use Hypertension: Withhold treatment in patients until both the systolic blood ALIQOPA safely and effectively. See full prescribing information for pressure (BP) is less than 150 mmHg and the diastolic BP is less than 90 ALIQOPA. mmHg. Consider reducing dose if anti-hypertensive treatment is required. Discontinue in patients with BP that is uncontrolled or with life-threatening ALIQOPA™ (copanlisib) for injection, for intravenous use consequences (5.3). Initial U.S. Approval: 2017 Non-infectious pneumonitis (NIP): Treat NIP and reduce dose. Discontinue --------------------------- INDICATIONS AND USAGE ---------------------------- treatment if Grade 2 NIP recurs or in patients experiencing Grade 3 or higher NIP (5.4). ALIQOPA is a kinase inhibitor indicated for the treatment of adult patients with relapsed follicular lymphoma (FL) who have received at least two prior Neutropenia: Monitor blood counts at least weekly while under treatment. systemic therapies (1). Withhold treatment until ANC ≥0.5 x 103 cells/mm3 (5.5). Accelerated approval was granted for this indication based on overall response Severe Cutaneous Reactions: Withhold treatment, reduce dose, or rate. Continued approval for this indication may be contingent upon discontinue treatment depending on the severity and persistence of severe verification and description of clinical benefit in a confirmatory trial. cutaneous reactions (5.6). Embryo-Fetal Toxicity: ALIQOPA can cause fetal harm. Advise patients of ----------------------- DOSAGE AND ADMINISTRATION ----------------------- potential risk to a fetus and to use effective contraception (5.7, 8.1, 8.3). Recommended dosage: 60 mg administered as a 1-hour intravenous ------------------------------ ADVERSE REACTIONS ------------------------------ infusion on Days 1, 8, and 15 of a 28-day treatment cycle on an intermittent schedule (three weeks on and one week off).
    [Show full text]
  • Injectable and Health Care Administered Oncology Medical Drug Criteria Through Preferred (Optional)
    Injectable and Health Care Administered Oncology Medical Drug Program Summary For patients with late stage metastatic disease (Stage IV), please refer to MP 2.373 Step Therapy Treatment in Cancer, Including Treatments for Stage Four, Advanced Metastatic Cancer and Severe Related Health Conditions for additional guidance *No Preferred Strategy The clinical rationale section is inf ormational, please refer to the medical drug criteria section for agents requiring medical drug review. FDA APPROVED INDICATIONS AND DOSAGE1-65 Agent Indication Dosage Abraxane® [paclitaxel ● Metastatic breast cancer Metastatic breast cancer: (protein bound)] af ter failure of combination 260 mg/m2 intravenously chemotherapy or relapse over 30 minutes, every 3 Injectable suspension within 6 months of adjuvant weeks chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated ● Locally advanced or NSCLC: metastatic Non-Small Cell 100 mg/m2 intravenously Lung Cancer (NSCLC) as over 30 minutes on Days 1, f irst-line treatment in 8, and 15 of each 21-day combination with cycle. Administer carboplatin, in patients who carboplatin on Day 1 of each are not candidates for 21-day cycle immediately curative surgery or radiation af ter Abraxane therapy ● Metastatic adenocarcinoma Metastatic of the pancreas as first-line adenocarcinoma of the treatment in combination pancreas: with gemcitabine 125 mg/m2 intravenously over 30-40 minutes on Days 1, 8, and 15 of each 28-day cycle. Administer gemcitabine immediately af ter paclitaxel (protein bound) on days 1, 8, and 15 of each 28-day cycle Adcetris® (brentuximab Treatment of adult patients vedotin) with: Injection for intravenous ● Previously untreated Stage Previously untreated use III or IV classical Hodgkin Stage III or IV cHL: 1.2 lymphoma (cHL) in mg/kg up to a maximum of combination with 120 mg every 2 weeks for a doxorubicin, vinblastine, and maximum of 12 doses dacarbazine CBC_CS_Reg_MDC_Injectable_and_Health_Care_Administered_Oncology_P rogSum_AR0620_r0321 Page 1 of 46 © Copyright Prime Therapeutics LLC.
    [Show full text]