DOCSLIB.ORG

New Drug Updates Brendan Mangan, Pharmd Clinical Pharmacy Specialist Hospital of the University of Pennsylvania

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
New Drug Updates Brendan Mangan, Pharmd Clinical Pharmacy Specialist Hospital of the University of Pennsylvania 11/9/2020 Disclosures • There are no relevant financial interests to disclose for myself or my spouse/partner from within the last 12 months New Drug Updates Brendan Mangan, PharmD Clinical Pharmacy Specialist Hospital of the University of Pennsylvania 1 2 Objectives New Drugs Explain the pharmacology of each new medication Malignant Hematology Medical Oncology Define indications, adverse effects and pertinent drug interactions Outline supportive care measures and clinical pearls Selinexor Tazemotostat Isatuximab-irfc Avapritinib Discuss the results of clinical trials and place in therapy Belantamab mafodotin-blmf Pexidartinib Fedratinib Entrectinib Polatuzumab vedotin-piiq Tafasitamab-cxix Zanubrutinib 3 4 Selinexor (XPOVIO®) Approval: July 3, 2019 Novel agent Exportin 1 inhibitor ▫ Reversibly inhibits nuclear export of tumor suppressor proteins, growth regulators, and mRNAs of oncogenic proteins XPOVI™ [Prescribing Information] Newton, MA. Karyopharm Therapeutics. 2019. Picture: xpovio.com 5 6 1 11/9/2020 Selinexor Selinexor Indication Adverse Effects Clinical Pearls • In combination with dexamethasone for relapse refractory multiple myeloma after failing 4 prior therapies Thrombocytopenia (74%) GCSF and prophylactic antimicrobials Recommended Neutropenia (34%) Prophylactic anti-emetics First Reduction Second Reduction Third Reduction Starting Dosage Nausea (72%)/Vomiting (41%) IV fluids and electrolyte repletion may be Diarrhea (44%) warranted monitor closely 80 mg Discontinue Days 1 and 3 of each Anorexia (53%)/Weight loss (47%) Correct sodium levels for concurrent 100 mg once weekly 80 mg once weekly 60 mg once weekly week (160 mg weekly Hyponatremia (39%) hyperglycemia (>150 mg/dL) total) Infections (52%) TPO agonist may be warranted for Neurological toxicity (30%) thrombocytopenia GCSF = Granulocyte colony-stimulating factor XPOVI™ [Prescribing Information] Newton, MA. Karyopharm Therapeutics. 2019. XPOVI™ [Prescribing Information] Newton, MA. Karyopharm Therapeutics. 2019. TPO = Thrombopoietin receptor agonist 7 8 Selinexor – STORM Trial Isatuximab-irfc (Sarclisa®) Design • Approval: March 2, 2020 • Phase 2b, multicenter, open-label trial at 60 centers in the US and Europe • CD38-directed cytolytic Patients antibody • 122 patients with relapsed refractory multiple myeloma with previous exposure to bortezomib, ▫ CD38 expressed on the surface carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent of hematopoietic and tumor cells, including multiple Outcomes myeloma cells ▫ Induces apoptosis of tumor • ORR: 26% cells and activation of immune • Median duration of response: 4.4 months effector mechanisms • PFS: 3.7 months • OS: 8.6 months ORR = Overall response rate PFS = Progression free survival Chari A, et al. N Engl J Med. 2019. Sarclisa® [prescribing information]. Bridgewater, NJ. Sanofi. 2020. OS = Overall survival Picture: Frontiersin.org 9 10 Isatuximab-irfc Isatuximab-irfc Indication Adverse effects Clinical Pearls • In combination with pomalidomide and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a Premedication with acetaminophen, H2- Infusion-related reactions (38%) proteasome inhibitor antagonist, diphenhydramine and Pneumonia (31%) dexamethasone warranted. Dosing Upper respiratory tract infections (57%) Can cause a false positive indirect Coombs test • In combination with pomalidomide and dexamethasone- C1 10 mg/kg as an intravenous infusion Febrile neutropenia (12%) Prior to treatment, consider phenotyping every week x4 weeks, then every 2 weeks until disease progression or unacceptable toxicity Dyspnea (17%) May interfere with Serum Protein Diarrhea (26%) Electrophoresis and Immunofixation Tests Dose Adjustments Nausea (15%) / Vomiting (12%) May infuse more rapidly on third infusion • No dosage adjustments recommended. Dosages may be delayed to allow for recovery of blood counts in the event of hematologic toxicity (Neutropenia: ANC < 1000/mm3) Sarclisa® [prescribing information]. Bridgewater, NJ. Sanofi. 2020. Sarclisa® [prescribing information]. Bridgewater, NJ. Sanofi. 2020. 11 12 2 11/9/2020 Isatuximab-irfc Trial Belantamab mafodotin- Design blmf (Blenrep®) • Phase 3, randomized, double-blind, open-label trial • Approval: August 5, 2020 • Class: B-cell maturation antigen Patients (BCMA)-directed antibody drug conjugate • 307 patients with relapsed refractory multiple myeloma who received at least 2 prior therapies, ▫ Conjugated to a microtubule including lenalidomide and a proteasome inhibitor One patient in the isatuximab group was inhibitor previously treated with daratumumab ▫ Antibody is conjugated by a Outcomes protease-resistant maleimidocaproyl linker to • PFS: 11.53 months vs 6.46 months (p = 0.001) microtubule-disrupting • ORR: 60.4% vs 35.3 % (p < 0.001) monomethyl auristatin F • Median time to response was 35 days in isatuximab-irfc group compared to 58 days in the Pd (MMAF) arm *Pd = pomalidomide + dexamethasone Attal M, et al. Lancet. 2017. Blenrep® [prescribing information]. Research Triangle Park, NC. GlaxoSmithKline. 2020. Picture: Oncozine.com 13 14 Belantamab mafodotin-blmf Belantamab mafodotin-blmf Indication Adverse effects Clinical Pearls • Treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and Ophthalmic examinations at baseline, prior an immunomodulatory agent Ocular toxicity (77%) BBW Keratopathy to each dose, and for worsening symptoms. Dosing Must be within 3 weeks of first dose Visual Acuity Changes • 2.5 mg/kg as an IV infusion over approximately 30 minutes once every 3 weeks Administer preservative-free lubricant eye Thrombocytopenia (69%) drops at least 4 times daily starting first Infusion-related reactions (18%) infusion and until the end of treatment Dose Adjustments Avoid the use of contact lenses during treatment • Based on toxicity: Immunogenicity (<1%) • Grade 2-3: Hold until Grade 1 or better • Grade 4: Consider permanent discontinuation REMS Program BBW = Black box warning Blenrep® [prescribing information]. Research Triangle Park, NC. GlaxoSmithKline. 2020. Blenrep® [prescribing information]. Research Triangle Park, NC. GlaxoSmithKline. 2020. 15 16 Belantamab mafodotin-blmf: DREAMM-2 Trial Fedratinib (Inrebic®) Design • FDA Approval: August 16, 2019 • Phase 2, open-label, two-arm, study Patients • Class: JAK inhibitor ▫ Oral TKI with activity against • 221 adult patients with multiple myeloma with disease progression after three or more lines of both wild type and mutated therapy (refractory to immunomodulatory drugs, proteasome inhibitors, and anti-CD38 JAK2 and FLT3 monoclonal antibodies) Outcomes • Overall response rate: • 2.5 mg/kg group: 31% • 3.4 mg/kg group: 34% Lonial et al. Lancet. 2020 INREBIC™ [Prescribing Information] Summit, NJ, Celgene Corporation. 2019. Picture: sciencedirect.com 17 18 3 11/9/2020 Fedratinib Fedratinib Indication • Adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis Adverse effects Clinical Pearls Dosing Check thiamine levels and supplementation Encephalopathy (1.3%) BBW may be warranted • 400 mg daily in patients with baseline platelet count of > 50 x 10^9/L Anemia (74%) Must taper and discontinue ruxolitinib Dose Adjustments Thrombocytopenia (47%) according to package insert prior to starting • Reduce to 200 mg daily for: Neutropenia (23%) fedratinib • CrCl 15-20 ml/min Diarrhea (66%) Prophylactic anti-emetics may be warranted • Strong CYP3A4 inhibitors Nausea (62%)/Vomiting (39%) Monitor LFTs at baseline and when clinically • Reduce by 100 mg daily for: ALT (43%)/AST (40%) indicated • Grade 4 neutropenia once resolved to < 2 Amylase (2%) / Lipase (10%) Monitor amylase/lipase at baseline and when • Grade 3 AST/ALT once resolved to < 1 clinically indicated • Any grade 3 nonhematologic toxicity once resolved to < 1 BBW = Black box warning AST = Aspartate aminotransferase INREBIC™ [Prescribing Information] Summit, NJ, Celgene Corporation. 2019. ALT = Alanine aminotransferase INREBIC™ [Prescribing Information] Summit, NJ, Celgene Corporation. 2019. 19 20 Fedratinib: JAKARTA Trial Polatuzumab vedotin- piiq (POLIVY™) Design • Approval: June 10, 2019 • Phase 3, double-blind, placebo controlled trial Patients • Novel agent CD79b-directed antibody-drug conjugate • 289 patients not previously treated with a JAK inhibitor with intermediate-2 or high-risk primary ▫ Humanized IgG1 monoclonal or secondary myelofibrosis were randomized to receiver fedratinib 400 mg daily, fedratinib 500 antibody specific for CD79b mg daily, or placebo ▫ Small molecule anti-mitotic Outcomes agent MMAE ▫ A protease-cleavable linker • Spleen response at 6 months and confirmed 4 weeks later ( > 35% reduction in volume): maleimidocaproyl-valine- • 35% in 400 mg group citrulline-p- • 40% in 500 mg group 500 mg/day group: MRI confirmed aminobenzyloxycarbonyl that • 1% in placebo Wernicke encephalopathy in 4 covalently attaches MMAE to patients the polatuzumab antibody Pardanani A et al. JAMA Oncol. 2015. Polivy® [prescribing information]. San Francisco, CA: Genentech, Inc.: 2019 Picture: Polivy.com 21 22 Polatuzumab vedotin-piiq Polatuzumab vedotin-piiq Indication Adverse Effects (Incidence > 20%) Clinical Pearls • In combination with bendamustine and rituximab in adult patients with relapse or refractory DLBCL, not
Load more

Recommended publications
  • Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients
    antibodies Review Pharmacologic Considerations in the Disposition of Antibodies and Antibody-Drug Conjugates in Preclinical Models and in Patients Andrew T. Lucas 1,2,3,*, Ryan Robinson 3, Allison N. Schorzman 2, Joseph A. Piscitelli 1, Juan F. Razo 1 and William C. Zamboni 1,2,3 1 University of North Carolina (UNC), Eshelman School of Pharmacy, Chapel Hill, NC 27599, USA; [email protected] (J.A.P.); [email protected] (J.F.R.); [email protected] (W.C.Z.) 2 Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] 3 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-919-966-5242; Fax: +1-919-966-5863 Received: 30 November 2018; Accepted: 22 December 2018; Published: 1 January 2019 Abstract: The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution.
    [Show full text]
  • A Phase I Study of Pexidartinib, a Colony-Stimulating Factor 1 Receptor Inhibitor, in Asian Patients with Advanced Solid Tumors
    Investigational New Drugs https://doi.org/10.1007/s10637-019-00745-z PHASE I STUDIES A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors Jih-Hsiang Lee1 & Tom Wei-Wu Chen2 & Chih-Hung Hsu2,3 & Yu-Hsin Yen2 & James Chih-Hsin Yang2,3 & Ann-Lii Cheng2,3 & Shun-ichi Sasaki4 & LiYin (Lillian) Chiu5 & Masahiro Sugihara4 & Tomoko Ishizuka4 & Toshihiro Oguma4 & Naoyuki Tajima4 & Chia-Chi Lin2,6 Received: 15 January 2019 /Accepted: 7 February 2019 # The Author(s) 2019 Summary Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony- stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All11patients(6males,5 females; median age 64, range 23–82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransfer- ase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and800mg/dthereafter.Pexidartinibexposure,areaundertheplasmaconcentration-timecurvefromzeroto8h(AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses.
    [Show full text]
  • Press Release
    Press Release Daiichi Sankyo and AstraZeneca Announce Global Development and Commercialization Collaboration for Daiichi Sankyo’s HER2 Targeting Antibody Drug Conjugate [Fam-] Trastuzumab Deruxtecan (DS-8201) Collaboration combines Daiichi Sankyo’s scientific and technological excellence with AstraZeneca’s global experience and resources in oncology to accelerate and expand the potential of [fam-] trastuzumab deruxtecan as monotherapy and combination therapy across a spectrum of HER2 expressing cancers AstraZeneca to pay Daiichi Sankyo up to $6.90 billion in total consideration, including $1.35 billion upfront payment and up to an additional $5.55 billion contingent upon achievement of future regulatory and sales milestones as well as other contingencies Companies to share equally development and commercialization costs as well as profits worldwide from [fam-] trastuzumab deruxtecan with Daiichi Sankyo maintaining exclusive rights in Japan Daiichi Sankyo is expected to book sales in U.S., certain countries in Europe, and certain other markets where Daiichi Sankyo has affiliates; AstraZeneca is expected to book sales in all other markets worldwide, including China, Australia, Canada and Russia Tokyo, Munich and Basking Ridge, NJ – (March 28, 2019) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced today that it has entered into a global development and commercialization agreement with AstraZeneca for Daiichi Sankyo’s lead antibody drug conjugate (ADC), [fam-] trastuzumab deruxtecan (DS-8201), currently in pivotal development for multiple HER2 expressing cancers including breast and gastric cancer, and additional development in non-small cell lung and colorectal cancer. Daiichi Sankyo and AstraZeneca will jointly develop and commercialize [fam-] trastuzumab deruxtecan as a monotherapy or a combination therapy worldwide, except in Japan where Daiichi Sankyo will maintain exclusive rights.
    [Show full text]
  • Australian Public Assessment for Polatuzumab Vedotin
    Australian Public Assessment Report for Polatuzumab vedotin Proprietary Product Name: Polivy Sponsor: Roche Products Pty Ltd December 2019 Therapeutic Goods Administration About the Therapeutic Goods Administration (TGA) • The Therapeutic Goods Administration (TGA) is part of the Australian Government Department of Health and is responsible for regulating medicines and medical devices. • The TGA administers the Therapeutic Goods Act 1989 (the Act), applying a risk management approach designed to ensure therapeutic goods supplied in Australia meet acceptable standards of quality, safety and efficacy (performance) when necessary. • The work of the TGA is based on applying scientific and clinical expertise to decision- making, to ensure that the benefits to consumers outweigh any risks associated with the use of medicines and medical devices. • The TGA relies on the public, healthcare professionals and industry to report problems with medicines or medical devices. TGA investigates reports received by it to determine any necessary regulatory action. • To report a problem with a medicine or medical device, please see the information on the TGA website <https://www.tga.gov.au>. About AusPARs • An Australian Public Assessment Report (AusPAR) provides information about the evaluation of a prescription medicine and the considerations that led the TGA to approve or not approve a prescription medicine submission. • AusPARs are prepared and published by the TGA. • An AusPAR is prepared for submissions that relate to new chemical entities, generic medicines, major variations and extensions of indications. • An AusPAR is a static document; it provides information that relates to a submission at a particular point in time. • A new AusPAR will be developed to reflect changes to indications and/or major variations to a prescription medicine subject to evaluation by the TGA.
    [Show full text]
  • Pharmacokinetics of Polatuzumab Vedotin in Combination with R/G‑CHP in Patients with B‑Cell Non‑Hodgkin Lymphoma
    Cancer Chemotherapy and Pharmacology (2020) 85:831–842 https://doi.org/10.1007/s00280-020-04054-8 ORIGINAL ARTICLE Pharmacokinetics of polatuzumab vedotin in combination with R/G‑CHP in patients with B‑cell non‑Hodgkin lymphoma Colby S. Shemesh1 · Priya Agarwal1 · Tong Lu1 · Calvin Lee2 · Randall C. Dere3 · Xiaobin Li1 · Chunze Li1 · Jin Y. Jin1 · Sandhya Girish1 · Dale Miles1 · Dan Lu1 Received: 4 October 2019 / Accepted: 3 March 2020 / Published online: 28 March 2020 © The Author(s) 2020 Abstract Purpose The phase Ib/II open-label study (NCT01992653) evaluated the antibody-drug conjugate polatuzumab vedotin (pola) plus rituximab/obinutuzumab, cyclophosphamide, doxorubicin, and prednisone (R/G-CHP) as frst-line therapy for B-cell non-Hodgkin lymphoma (B-NHL). We report the pharmacokinetics (PK) and drug–drug interaction (DDI) for pola. Methods Six or eight cycles of pola 1.0–1.8 mg/kg were administered intravenously every 3 weeks (q3w) with R/G-CHP. Exposures of pola [including antibody-conjugated monomethyl auristatin E (acMMAE) and unconjugated MMAE] and R/G-CHP were assessed by non-compartmental analysis and/or descriptive statistics with cross-cycle comparisons to cycle 1 and/or after multiple cycles. Pola was evaluated as a potential victim and perpetrator of a PK drug–drug interaction with R/G-CHP. Population PK (popPK) analysis assessed the impact of prior treatment status (naïve vs. relapsed/refractory) on pola PK. Results Pola PK was similar between treatment arms and independent of line of therapy. Pola PK was dose proportional from 1.0 to 1.8 mg/kg with R/G-CHP.
    [Show full text]
  • Daiichi Sankyo Group Value Report 2019
    External Evaluations (as of June 30,2019) ™ Daiichi Sankyo Group Value Report 2019 Value Daiichi Sankyo Group MSCI Japan Empowering Women Select Index THE INCLUSION OF DAIICHI SANKYO CO.,LTD. IN ANY MSCI INDEX, AND THE USE OF MSCI LOGOS, TRADEMARKS, SERVICE MARKS OR INDEX NAMES HEREIN, DO NOT CONSTITUTE A SPONSORSHIP, ENDORSEMENT OR PROMOTION OF DAIICHI SANKYO CO.,LTD. BY MSCI OR ANY OF ITS AFFILIATES. THE MSCI INDEXES ARE THE EXCLUSIVE PROPERTY OF MSCI. MSCI AND THE MSCI INDEX NAMES AND LOGOS ARE TRADE- MARKS OR SERVICE MARKS OF MSCI OR ITS AFFILIATES. “Eruboshi” Certification Mark “Kurumin” Certification Mark Logo given to Certified Health and Productivity Management Organization (White500) This report uses FSC® certified paper, which indicates that the paper used to print this Paper report was produced from properly managed forests. 3-5-1, Nihonbashi-honcho, Chuo-ku, Tokyo 103-8426, Japan This report was printed using 100% Inks biodegradable printing inks from vegetable Corporate Communications Department oil. Daiichi Sankyo Group Tel: +81-3-6225-1126 CSR Department The waterless printing method used for this Value Report 2019 Tel: +81-3-6225-1067 Printing report minimized the use and release of harmful liquid wastes. https://www.daiichisankyo.com/ Printed in Japan 005_7045687911909.indd 1 2019/09/27 18:22:19 Introduction Our Mission The Core Values and Commitments serve as the criteria for business activities and In addition, we have established the DAIICHI SANKYO Group Corporate Conduct Charter . decision-making used by executive officers and employees in working to fulfill Our Mission . This charter calls on us to fulfill our social responsibilities by acting with the highest ethical Our Corporate Slogan succinctly explains the spirit of Our Mission, Core Values and standards and a good social conscience appropriate for a company engaged in business Commitments.
    [Show full text]
  • The Tumor Microenvironment and Overcoming Immune Escape Arsen Osipov1, May Tun Saung1, Lei Zheng1 and Adrian G
    Osipov et al. Journal for ImmunoTherapy of Cancer (2019) 7:224 https://doi.org/10.1186/s40425-019-0667-0 REVIEW Open Access Small molecule immunomodulation: the tumor microenvironment and overcoming immune escape Arsen Osipov1, May Tun Saung1, Lei Zheng1 and Adrian G. Murphy1,2* Abstract Immunotherapy has led to a paradigm shift in the treatment of many advanced malignancies. Despite the success in treatment of tumors like non-small cell lung cancer (NSCLC) and melanoma, checkpoint inhibition-based immunotherapy has limitations. Many tumors, such as pancreatic cancer, are less responsive to checkpoint inhibitors, where patients tend to have a limited duration of benefit and where clinical responses are more robust in patients who are positive for predictive biomarkers. One of the critical factors that influence the efficacy of immunotherapy is the tumor microenvironment (TME), which contains a heterogeneous composition of immunosuppressive cells. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) alter the immune landscape of the TME and serve as facilitators of tumor proliferation, metastatic growth and immunotherapy resistance. Small molecule inhibitors that target these components of the TME have been developed. This special issue review focuses on two promising classes of immunomodulatory small molecule inhibitors: colony stimulating factor-1 receptor (CSF-1R) and focal adhesion kinase (FAK). Small molecule inhibitors of CSF-1R reprogram the TME and TAMs, and lead to enhanced T-cell-mediated tumor eradication. FAK small molecule inhibitors decrease the infiltration MDSCs, TAMs and regulatory T-cells. Additionally, FAK inhibitors are implicated as modulators of stromal density and cancer stem cells, leading to a TME more conducive to an anti-tumor immune response.
    [Show full text]
  • Antibody–Drug Conjugates
    Published OnlineFirst April 12, 2019; DOI: 10.1158/1078-0432.CCR-19-0272 Review Clinical Cancer Research Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index Steven Coats1, Marna Williams1, Benjamin Kebble1, Rakesh Dixit1, Leo Tseng1, Nai-Shun Yao1, David A. Tice1, and Jean-Charles Soria1,2 Abstract Since the first approval of gemtuzumab ozogamicin nism of activity of the cytotoxic warhead. However, the (Mylotarg; Pfizer; CD33 targeted), two additional antibody– enthusiasm to develop ADCs has not been dampened; drug conjugates (ADC), brentuximab vedotin (Adcetris; Seat- approximately 80 ADCs are in clinical development in tle Genetics, Inc.; CD30 targeted) and inotuzumab ozogami- nearly 600 clinical trials, and 2 to 3 novel ADCs are likely cin (Besponsa; Pfizer; CD22 targeted), have been approved for to be approved within the next few years. While the hematologic cancers and 1 ADC, trastuzumab emtansine promise of a more targeted chemotherapy with less tox- (Kadcyla; Genentech; HER2 targeted), has been approved to icity has not yet been realized with ADCs, improvements treat breast cancer. Despite a clear clinical benefit being dem- in technology combined with a wealth of clinical data are onstrated for all 4 approved ADCs, the toxicity profiles are helping to shape the future development of ADCs. In this comparable with those of standard-of-care chemotherapeu- review, we discuss the clinical and translational strategies tics, with dose-limiting toxicities associated with the mecha- associated with improving the therapeutic index for ADCs. Introduction in antibody, linker, and warhead technologies in significant depth (2, 3, 8, 9). Antibody–drug conjugates (ADC) were initially designed to leverage the exquisite specificity of antibodies to deliver targeted potent chemotherapeutic agents with the intention of improving Overview of ADCs in Clinical Development the therapeutic index (the ratio between the toxic dose and the Four ADCs have been approved over the last 20 years (Fig.
    [Show full text]
  • Federal Register Notice 5-1-2020 Pdf Icon[PDF – 358
    Federal Register / Vol. 85, No. 85 / Friday, May 1, 2020 / Notices 25439 confidential by the respondent (5 U.S.C. schedules. Other than examination DEPARTMENT OF HEALTH AND 552(b)(4)). reports, it provides the only financial HUMAN SERVICES Current actions: The Board has data available for these corporations. temporarily revised the instructions to The Federal Reserve is solely Centers for Disease Control and the FR Y–9C report to accurately reflect responsible for authorizing, supervising, Prevention the revised definition of ‘‘savings and assigning ratings to Edges. The [CDC–2020–0046; NIOSH–233–C] deposits’’ in accordance with the Federal Reserve uses the data collected amendments to Regulation D in the on the FR 2886b to identify present and Hazardous Drugs: Draft NIOSH List of interim final rule published on April 28, potential problems and monitor and Hazardous Drugs in Healthcare 2020 (85 FR 23445). Specifically, the develop a better understanding of Settings, 2020; Procedures; and Risk Board has temporarily revised the activities within the industry. Management Information instructions on the FR Y–9C, Schedule HC–E, items 1(b), 1(c), 2(c) and glossary Legal authorization and AGENCY: Centers for Disease Control and content to remove the transfer or confidentiality: Sections 25 and 25A of Prevention, HHS. withdrawal limit. As a result of the the Federal Reserve Act authorize the ACTION: Notice and request for comment. revision, if a depository institution Federal Reserve to collect the FR 2886b chooses to suspend enforcement of the (12 U.S.C. 602, 625). The obligation to SUMMARY: The National Institute for six transfer limit on a ‘‘savings deposit,’’ report this information is mandatory.
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • Belantamab Mafodotin (Blenrep) Reference Number: ERX.SPA.383 Effective Date: 08.05.20 Last Review Date: 05.21 Line of Business: Commercial, Medicaid Revision Log
    Clinical Policy: Belantamab Mafodotin (Blenrep) Reference Number: ERX.SPA.383 Effective Date: 08.05.20 Last Review Date: 05.21 Line of Business: Commercial, Medicaid Revision Log See Important Reminder at the end of this policy for important regulatory and legal information. Description Belantamab mafodotin (Blenrep®) is an anti-B-cell maturation antigen (BCMA) monoclonal antibody and microtubule inhibitor conjugate. FDA Approved Indication(s) Blenrep is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including an anti-CD38 antibody, a proteasome inhibitor, and an immunomodulatory agent. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria. Health plan approved formularies should be reviewed for all coverage determinations. Requirements to use preferred alternative agents apply only when such requirements align with the health plan approved formulary. It is the policy of health plans affiliated with Envolve Pharmacy Solutions™ that Blenrep is medically necessary when the following criteria are met: I. Initial Approval Criteria A. Multiple Myeloma (must meet all): 1. Diagnosis of multiple myeloma; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥ 18 years; 4. Blenrep is prescribed as monotherapy; 5. Member has received ≥ 4 prior lines of therapy (see Appendix B for examples) that include all of the following (a, b, and c): a.
    [Show full text]
  • Disease(S) Brand Name Drug Name Drug Company Phone Number Website Calaspargase No Financial Assistance Offered at This Asparlas Servier Pegol-Mknl Time
    Co-Pay Assistance Resource Guide for Blood Cancer Patients Acute Lymphoblastic Leukemia (ALL) Disease(s) Brand Name Drug Name Drug Company Phone Number Website calaspargase No financial assistance offered at this Asparlas Servier pegol-mknl time. https://www.pfizertogether.com/hcp/bes BESPONSA Ozogamicin Wyeth 1-877-744-5675 ponsa/patient-financial-assistance Acute Lymphoblastic http://www.amgen.com/responsibility/ac Leukemia (ALL) - B- cess-to-medicine/reimbursement- Blincyto Blinatumomab Amgen 1-855-669-9360 cell Precursor support-services-and-financial- assistance-programs/ https://www.hcp.novartis.com/products/k Kymriah Tisagenlecleucel Novartis 1-844-459-6742 ymriah/acute-lymphoblastic-leukemia- children/access/ http://www.oncologyaccessnow.com/ind Gleevec® Imatinib Mesylate Novartis 1-800-282-7630 ex.jsp *not offering patient assistance nor cost savings program* Gleevec® Generic Imatinib Mesylate Teva 1-844-546-8639 https://www.tevagenerics.com/patients/fr Ph+ Acute equently-asked-questions/#q-1-1 Lymphoblastic Generic Imatinib Imatinib Mesylate Sun Pharma 1/844-502-5950 https://rxoutreach.org/ Leukemia (ALL) https://www.takedaoncology1point.com/ Iclusig® Ponatinib Takeda 1-844-817-6468 patient/financial-assistance Bristol-Myers Sprycel® Dasatinib 1-877-526-7334 https://www.sprycel.com/sprycel-assist Squibb Trisenox Arsenic Trioxide Teva 1-877-237-4881 http://www.tevacares.org/ http://www.amgen.com/responsibility/ac Acute Lymphoblastic cess-to-medicine/reimbursement- Leukemia (ALL) Blincyto Blinatumomab Amgen 1-855-669-9360 support-services-and-financial-
    [Show full text]