DOCSLIB.ORG

Daiichi Sankyo Oncologic Drugs Advisory Committee Briefing Document for the May 14, 2019, Us Fda Oncologic Drugs Advisory Commit

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Daiichi Sankyo Oncologic Drugs Advisory Committee Briefing Document for the May 14, 2019, Us Fda Oncologic Drugs Advisory Commit DAIICHI SANKYO ONCOLOGIC DRUGS ADVISORY COMMITTEE BRIEFING DOCUMENT FOR THE MAY 14, 2019, US FDA ONCOLOGIC DRUGS ADVISORY COMMITTEE MEETING TURALIO (PEXIDARTINIB) CAPSULES NDA 211810 INDICATION: TENOSYNOVIAL GIANT CELL TUMOR DATE FINALIZED: APRIL 11, 2019 AVAILABLE FOR PUBLIC DISCLOSURE WITHOUT REDACTION Daiichi Sankyo, Inc. 211 Mt. Airy Road Basking Ridge, NJ 07920 United States Pexidartinib NDA 211810 FDA Advisory Committee Briefing Document Daiichi Sankyo April 11, 2019 TABLE OF CONTENTS 1 EXECUTIVE SUMMARY ...................................................................................................10 1.1 Overview .........................................................................................................................10 1.2 Proposed Indication and Dose ........................................................................................11 1.3 Disease Background and Unmet Medical Need .............................................................11 1.4 Pexidartinib Development Rationale ..............................................................................13 1.5 Pexidartinib Clinical Development Program ..................................................................14 1.5.1 Summary of Clinical Pharmacology ...................................................................14 1.5.2 Summary of Clinical Efficacy ............................................................................15 1.5.2.1 Phase 3 Study PLX108-10 (ENLIVEN) ..............................................15 1.5.2.1.1 Study Design ..................................................................... 15 1.5.2.1.2 Results ............................................................................... 17 1.5.2.1.3 Primary Efficacy Endpoint Results ................................... 18 1.5.2.1.4 Secondary Efficacy Endpoint Results ............................... 18 1.5.2.1.5 Efficacy With Longer Pexidartinib Treatment ................. 20 1.5.2.2 Phase 1 Study PLX108-01 (TGCT Extension Cohort) ........................20 1.5.2.3 Efficacy Conclusions ...........................................................................20 1.5.3 Summary of Clinical Safety ................................................................................20 1.5.3.1 Exposure ..............................................................................................21 1.5.3.2 Treatment-Emergent Adverse Events ..................................................21 1.5.3.2.1 Adverse Events of Special Interest: Hepatic Adverse Reactions ........................................................................... 22 1.5.3.3 Safety Conclusions...............................................................................24 1.5.4 Dose Justification ................................................................................................24 1.6 Risk Evaluation and Mitigation Strategy ........................................................................24 1.7 Benefit:Risk Assessment ................................................................................................25 2 BACKGROUND AND SCIENTIFIC RATIONALE .........................................................26 2.1 Overview of Tenosynovial Giant Cell Tumor ................................................................26 2.1.1 Unmet Medical Need ..........................................................................................29 2.1.2 Role of CSF-1 in Tenosynovial Giant Cell Tumor .............................................30 3 PEXIDARTINIB OVERVIEW ............................................................................................32 3.1 Drug Description and Mechanism of Action ..................................................................32 3.2 Proposed Indication and Dose ........................................................................................34 3.2.1 Indication ............................................................................................................34 3.2.2 Dosage and Administration ................................................................................34 4 PEXIDARTINIB DEVELOPMENT PROGRAM..............................................................35 4.1 Regulatory History ..........................................................................................................35 4.2 Nonclinical Overview .....................................................................................................35 4.3 Clinical Development Overview ....................................................................................37 5 CLINICAL PHARMACOLOGY .........................................................................................39 5.1 Single- and Multiple-Dose Pharmacokinetics of Pexidartinib .......................................39 5.2 Metabolism and Transporter Studies ..............................................................................40 5.3 Effect of Intrinsic and Extrinsic Factors on the PK of Pexidartinib ...............................41 5.3.1 Effect of Intrinsic Factors ...................................................................................41 5.3.1.1 Demographic Characteristics (Age, Race/Ethnicity, Weight, Sex) .....41 5.3.1.2 Effect of Hepatic Impairment ..............................................................41 Page 2 of 108 Pexidartinib NDA 211810 FDA Advisory Committee Briefing Document Daiichi Sankyo April 11, 2019 5.3.1.3 Effect of Renal Impairment .................................................................41 5.4 Effect of UGT1A4 Polymorphism ..................................................................................41 5.4.1 Effect of Extrinsic Factors ..................................................................................42 5.4.1.1 Effect of Food, Gastric pH Modification, and Drug-Drug Interaction 42 5.5 Effect of Pexidartinib on QTc Interval ...........................................................................44 5.6 Clinical Pharmacology Conclusions ...............................................................................45 6 CLINICAL EFFICACY ........................................................................................................46 6.1 Phase 3 Study PLX108-10 (ENLIVEN) .........................................................................46 6.1.1 Study Design and Methods .................................................................................46 6.1.1.1 Dose Selection .....................................................................................48 6.1.1.2 Key Eligibility Criteria ........................................................................49 6.1.1.3 Statistical Analysis Methods ................................................................49 6.1.1.3.1 Sample Size Determination............................................... 49 6.1.1.3.2 Primary and Secondary Efficacy Analyses ....................... 49 6.1.2 Patient Disposition and Analysis Sets ................................................................50 6.1.3 Demographic and Other Baseline Characteristics ..............................................51 6.1.3.1 Demographic and Disease Characteristics ...........................................51 6.1.3.2 Prior Treatment ....................................................................................53 6.1.4 Efficacy Results ..................................................................................................54 6.1.4.1 Primary Efficacy Endpoint Tumor Response ......................................54 6.1.4.2 Secondary Efficacy Endpoints .............................................................56 6.1.4.3 Missing Clinical Outcomes Assessment Data and Sensitivity Analyses ..............................................................................................................57 6.1.4.3.1 Prespecified Sensitivity Analyses ..................................... 58 6.1.4.3.2 Post Hoc Sensitivity Analyses .......................................... 59 6.1.4.4 Efficacy With Longer Pexidartinib Treatment ....................................60 6.1.4.5 Efficacy Subgroup Analyses ................................................................63 6.2 Phase 1 Study PLX108-01 (TGCT Extension Cohort) ...................................................65 6.2.1 Study Design and Methods .................................................................................65 6.2.2 Patient Disposition ..............................................................................................66 6.2.3 Demographic and Other Baseline Characteristics ..............................................66 6.2.4 Efficacy Results ..................................................................................................66 6.2.4.1 Tumor Response ..................................................................................66 6.2.4.2 Central Review Tumor Response by RECIST v1.1 and Tumor Volume Score ....................................................................................................67 6.3 Efficacy Across the TGCT Population ...........................................................................67 6.4 Overall Efficacy Conclusions .........................................................................................71 7 CLINICAL SAFETY .............................................................................................................72 7.1 Safety Datasets ................................................................................................................72
Load more

Recommended publications
  • 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]
  • 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]
  • 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]
  • Phase Ib Study of the Combination of Pexidartinib (PLX3397), a CSF-1R Inhibitor, and Paclitaxel in Patients with Advanced Solid
    TAM0010.1177/1758835919854238Therapeutic Advances in Medical OncologyR Wesolowski, N Sharma 854238research-article20192019 Therapeutic Advances in Medical Oncology Original Research Ther Adv Med Oncol Phase Ib study of the combination of 2019, Vol. 11: 1 –13 DOI:https://doi.org/10.1177/1758835919854238 10.1177/ pexidartinib (PLX3397), a CSF-1R inhibitor, 1758835919854238https://doi.org/10.1177/1758835919854238 © The Author(s), 2019. Article reuse guidelines: and paclitaxel in patients with advanced sagepub.com/journals- solid tumors permissions Robert Wesolowski, Neelesh Sharma, Laura Reebel, Mary Beth Rodal, Alexandra Peck, Brian L. West, Adhirai Marimuthu, Paul Severson, David A. Karlin, Afshin Dowlati, Mai H. Le, Lisa M. Coussens and Hope S. Rugo Abstract Purpose: To evaluate the safety, recommended phase II dose (RP2D) and efficacy of pexidartinib, a colony stimulating factor receptor 1 (CSF-1R) inhibitor, in combination with weekly paclitaxel in patients with advanced solid tumors. Patients and Methods: In part 1 of this phase Ib study, 24 patients with advanced solid tumors received escalating doses of pexidartinib with weekly paclitaxel (80 mg/m2). Pexidartinib was administered at 600 mg/day in cohort 1. For subsequent cohorts, the dose was increased by ⩽50% using a standard 3+3 design. In part 2, 30 patients with metastatic solid tumors were enrolled to examine safety, tolerability and efficacy of the RP2D. Pharmacokinetics and biomarkers were also assessed. Results: A total of 51 patients reported ≥1 adverse event(s) (AEs) that were at least possibly related to either study drug. Grade 3–4 AEs, including anemia (26%), neutropenia (22%), lymphopenia (19%), fatigue (15%), and hypertension (11%), were Correspondence to: Robert Wesolowski recorded in 38 patients (70%).
    [Show full text]
  • CDER Breakthrough Therapy Designation Approvals Data As of December 31, 2020 Total of 190 Approvals
    CDER Breakthrough Therapy Designation Approvals Data as of December 31, 2020 Total of 190 Approvals Submission Application Type and Proprietary Approval Use Number Number Name Established Name Applicant Date Treatment of patients with previously BLA 125486 ORIGINAL-1 GAZYVA OBINUTUZUMAB GENENTECH INC 01-Nov-2013 untreated chronic lymphocytic leukemia in combination with chlorambucil Treatment of patients with mantle cell NDA 205552 ORIGINAL-1 IMBRUVICA IBRUTINIB PHARMACYCLICS LLC 13-Nov-2013 lymphoma (MCL) Treatment of chronic hepatitis C NDA 204671 ORIGINAL-1 SOVALDI SOFOSBUVIR GILEAD SCIENCES INC 06-Dec-2013 infection Treatment of cystic fibrosis patients age VERTEX PHARMACEUTICALS NDA 203188 SUPPLEMENT-4 KALYDECO IVACAFTOR 21-Feb-2014 6 years and older who have mutations INC in the CFTR gene Treatment of previously untreated NOVARTIS patients with chronic lymphocytic BLA 125326 SUPPLEMENT-60 ARZERRA OFATUMUMAB PHARMACEUTICALS 17-Apr-2014 leukemia (CLL) for whom fludarabine- CORPORATION based therapy is considered inappropriate Treatment of patients with anaplastic NOVARTIS lymphoma kinase (ALK)-positive NDA 205755 ORIGINAL-1 ZYKADIA CERITINIB 29-Apr-2014 PHARMACEUTICALS CORP metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib Treatment of relapsed chronic lymphocytic leukemia (CLL), in combination with rituximab, in patients NDA 206545 ORIGINAL-1 ZYDELIG IDELALISIB GILEAD SCIENCES INC 23-Jul-2014 for whom rituximab alone would be considered appropriate therapy due to other co-morbidities
    [Show 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.
    [Show full text]
  • Journal ONKO | Druckansicht
    01. Juni 2018 Präsentation neuer Daten zu den Antikörper-Arzneistoff- Konjugaten DS-8201 und U3-1402 Daiichi Sankyo gab bekannt, dass beim ASCO neue Daten zu zahlreichen in Erforschung befindlichen Wirkstoffen präsentiert werden. Zu den wichtigsten Highlights zählen neue Ergebnisse einer großen, laufenden Phase-I-Studie zu DS-8201 – einem gegen HER2 gerichteten Antikörper-Arzneistoff-Konjugaten (ADC) – bei metastasiertem Brustkrebs, Magenkrebs und anderen Tumoren mit HER2 als Zelloberflächen-Zielmolekül. Außerdem werden erste klinische Daten einer Phase-I-Studie zu U3- 1402 – einem gegen HER3 gerichteten, potentiellen first-in-class ADC – bei metastasiertem Brustkrebs mit HER3 als Zelloberflächen-Zielmolekül vorgestellt. Des Weiteren werden Ergebnisse der Placebo-kontrollierten Phase-III- Zulassungsstudie ENLIVEN zu Pexidartinib bei tenosynovialen Riesenzelltumoren (TGCT), auch bekannt als Riesenzelltumor der Sehnenschiede (GCT-TS) und früher als pigmentierte villonoduläre Synovialitis (PVNS) bezeichnet, einem seltenen Tumor des Gelenks oder der Sehnenscheide, präsentiert. Investigational ADC Franchise Presentations Trastuzumab deruxtecan (DS-8201a) in subjects with HER2-expressing solid tumors: Long-term results of a large phase 1 study with multiple expansion cohorts. (Abstract 2501; Oral Presentation; Friday, June 1 at 2:57- 3:09 PM CDT) A phase 2, multicenter, open-label study of trastuzumab deruxtecan (DS-8201a) in subjects with HER2-positive, unresectable and/or metastatic breast cancer previously treated with T-DM1. (Abstract TPS1102; Poster Session; Saturday, June 2 at 8:00-11:30 AM CDT) A randomized phase 2, multicenter, open-label study of trastuzumab deruxtecan (DS-8201a) in subjects with HER2- expressing gastric cancer. (Abstract TPS4133; Poster Session; Sunday, June 3 at 8:00-11:30 AM CDT) Single agent activity of U3-1402, a HER3-targeting antibody-drug conjugate, in breast cancer patients: phase 1 dose escalation study.
    [Show full text]
  • TURALIO (Pexidartinib) RATIONALE for INCLUSION in PA PROGRAM
    TURALIO (pexidartinib) RATIONALE FOR INCLUSION IN PA PROGRAM Background Turalio (pexidartinib) is a tyrosine kinase inhibitor that targets colony stimulating factor 1 receptor (CSF1R), KIT proto-oncogene receptor tyrosine kinase (KIT), and FMS-like tyrosine kinase 3 (FLT3) harboring an internal tandem duplication (ITD) mutation. Overexpression of the CSF1R ligand promotes cell proliferation and accumulation in the synovium (1). Regulatory Status FDA Approved Indication: Turalio is a kinase inhibitor indicated for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amendable to improvement with surgery (1). Turalio can cause serious and potentially fatal liver injury and is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Patient’s liver tests must be monitored prior to initiation of Turalio and at specified intervals during treatment (including every week for the first 8 weeks of treatment, every 2 weeks for the next month, and every 3 months thereafter). Consider withholding, dose reducing, or permanently discontinuing Turalio based on severity of hepatotoxicity (1). Females of reproductive potential should be advised to avoid becoming pregnant while being treated, as Turalio may cause fetal harm. Females of reproductive potential should be advised to use effective contraception during treatment with Turalio and for 1 month after the last dose. Males with a female partner of reproductive potential should be advised to use effective contraception during treatment with Turalio and for 1 week after the last dose (1). The safety and effectiveness of Turalio in pediatric patients less than 18 years of age have not been established (1).
    [Show full text]
  • Daiichi Sankyo Group Value Report 2018
    External Evaluations (as of June 30,2018) ™ 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 CON- STITUTE A SPONSORSHIP, ENDORSEMENT OR PROMOTION OF DAIICHI SANKYO CO.,LTD. BY MSCI OR ANY OF ITS AF- FILIATES. THE MSCI INDEXES ARE THE EXCLUSIVE PROP- ERTY OF MSCI. MSCI AND THE MSCI INDEX NAMES AND LOGOS ARE TRADEMARKS OR SERVICE MARKS OF MSCI OR ITS AFFILIATES. Daiichi Sankyo Group Value Report 2018 Value Daiichi Sankyo Group Logo given to Certified Health and Productivity Management “Eruboshi” Certification Mark “Kurumin” Certification Mark Organization (White500) Value Report 2018 was printed using environmental-friendly paper, inks, and manufacturing method. This report uses FSC® certified 3-5-1, Nihonbashi-honcho, Chuo-ku, paper, which indicates that the paper used to print this report Tokyo 103-8426, Japan Paper was produced from properly Daiichi Sankyo Group Corporate Communications Department managed forests. Tel: +81-3-6225-1126 Value Report 2018 CSR Department This report was printed using Tel: +81-3-6225-1067 Inks 100% biodegradable printing inks from vegetable oil. https://www.daiichisankyo.com/ The waterless printing method Printing used for this report minimized the use and release of harmful liquid wastes. Printed in Japan 005_7045687913009.indd 1 2018/09/13 13:34:05 Cautionary Note Regarding Forward-Looking Editorial Policy Company’s website https://www.daiichisankyo.com/ Statements Management strategies and plans, financial Daiichi Sankyo began publishing Value Reports, its brand of integrated reports, in fiscal 2013.
    [Show full text]
  • Negative Change Add Inclusion Criteria
    Policy Drug(s) Type of Change Brief Description of Policy Change new policy Elitek (rasburicase) n/a n/a new policy Retevmo (selpercatinib) n/a n/a new policy Tabrecta (capmatinib) n/a n/a new policy Trodelvy (govitecan-hziy) n/a n/a new policy Qinlock (ripretinib) n/a n/a UM ONC_1048 Campath (alemtuzumab) Archive Campath is no longer being used for any Hematology Oncology indications. Remove inclusion criteria: ALL: Induction, consolidation, maitenance, relapsed/refractory combination removed and use is supported as a part of a multi-agent chemotherapy regimen, for all sub-types of ALL, for induction/consolidation therapy, and for therapy of relapsed refractory disease NHL: Induction, consolidation, maitenance, relapsed/refractory combination removed and use is supported for extra- nodal NK/T-cell lymphoma (nasal type) and as a part of a multi-agent chemotherapy regimen for either first line therapy and/or therapy for relapsed /refractory disease. UM ONC_1063 Oncaspar (pegaspargase) Positive change Remove exclusion criteria: History of serious thrombosis, pancreatitis, or hemorrhagic events with L-asparaginase (ELSPAR) therapy. UM ONC_1064 Oncaspar (pegaspargase) Positive change Add exclusion criteria: Dosing exceeds single dose limit of Trastuzumab 8 mg/kg for the loading dose, 6 mg/kg for UM ONC_1134 Trastuzumab products Negative change subsequent doses when given every 3 weeks; 4 mg/kg for the loading dose and 2 mg/kg for the weekly dose. Remove exclusion criteria: Velcade (bortezomib) is being used after disease progression on another Velcade-based regimen. UM ONC_1136 Velcade (bortezomib) Positive change Add inclusion criteria: Multiple Myeloma: - NOTE: The preferred agent, per NCH policy, is generic bortezomib over brand bortezomib (Velcade) for all indications, unless there are contraindications or intolerance to generic bortezomib.
    [Show full text]