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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. -
07052020 MR ASCO20 Curtain Raiser
Media Release New data at the ASCO20 Virtual Scientific Program reflects Roche’s commitment to accelerating progress in cancer care First clinical data from tiragolumab, Roche’s novel anti-TIGIT cancer immunotherapy, in combination with Tecentriq® (atezolizumab) in patients with PD-L1-positive metastatic non- small cell lung cancer (NSCLC) Updated overall survival data for Alecensa® (alectinib), in people living with anaplastic lymphoma kinase (ALK)-positive metastatic NSCLC Key highlights to be shared on Roche’s ASCO virtual newsroom, 29 May 2020, 08:00 CEST Basel, 7 May 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that new data from clinical trials of 19 approved and investigational medicines across 21 cancer types, will be presented at the ASCO20 Virtual Scientific Program organised by the American Society of Clinical Oncology (ASCO), which will be held 29-31 May, 2020. A total of 120 abstracts that include a Roche medicine will be presented at this year's meeting. "At ASCO, we will present new data from many investigational and approved medicines across our broad oncology portfolio," said Levi Garraway, M.D., Ph.D., Roche's Chief Medical Officer and Head of Global Product Development. “These efforts exemplify our long-standing commitment to improving outcomes for people with cancer, even during these unprecedented times. By integrating our medicines and diagnostics together with advanced insights and novel platforms, Roche is uniquely positioned to deliver the healthcare solutions of the future." Together with its partners, Roche is pioneering a comprehensive approach to cancer care, combining new diagnostics and treatments with innovative, integrated data and access solutions for approved medicines that will both personalise and transform the outcomes of people affected by this deadly disease. -
Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy
Published OnlineFirst October 4, 2013; DOI: 10.1158/1078-0432.CCR-13-0358 Clinical Cancer Cancer Therapy: Clinical Research See related article by Gwin and Spector, p. 278 Dual Targeting of HER2-Positive Cancer with Trastuzumab Emtansine and Pertuzumab: Critical Role for Neuregulin Blockade in Antitumor Response to Combination Therapy Gail D. Lewis Phillips1, Carter T. Fields1, Guangmin Li1, Donald Dowbenko1, Gabriele Schaefer1, Kathy Miller5, Fabrice Andre6, Howard A. Burris III8, Kathy S. Albain9, Nadia Harbeck10, Veronique Dieras7, Diana Crivellari11, Liang Fang2, Ellie Guardino3, Steven R. Olsen3, Lisa M. Crocker4, and Mark X. Sliwkowski1 Abstract Purpose: Targeting HER2 with multiple HER2-directed therapies represents a promising area of treatment for HER2-positive cancers. We investigated combining the HER2-directed antibody–drug con- jugate trastuzumab emtansine (T-DM1) with the HER2 dimerization inhibitor pertuzumab (Perjeta). Experimental Design: Drug combination studies with T-DM1 and pertuzumab were performed on cultured tumor cells and in mouse xenograft models of HER2-amplified cancer. In patients with HER2- positive locally advanced or metastatic breast cancer (mBC), T-DM1 was dose-escalated with a fixed standard pertuzumab dose in a 3þ3 phase Ib/II study design. Results: Treatment of HER2-overexpressing tumor cells in vitro with T-DM1 plus pertuzumab resulted in synergistic inhibition of cell proliferation and induction of apoptotic cell death. The presence of the HER3 ligand, heregulin (NRG-1b), reduced the cytotoxic activity of T-DM1 in a subset of breast cancer lines; this effect was reversed by the addition of pertuzumab. Results from mouse xenograft models showed enhanced antitumor efficacy with T-DM1 and pertuzumab resulting from the unique antitumor activities of each agent. -
Trastuzumab and Paclitaxel in Patients with EGFR Mutated NSCLC That Express HER2 After Progression on EGFR TKI Treatment
www.nature.com/bjc ARTICLE Clinical Study Trastuzumab and paclitaxel in patients with EGFR mutated NSCLC that express HER2 after progression on EGFR TKI treatment Adrianus J. de Langen1,2, M. Jebbink1, Sayed M. S. Hashemi2, Justine L. Kuiper2, J. de Bruin-Visser2, Kim Monkhorst3, Erik Thunnissen4 and Egbert F. Smit1,2 BACKGROUND: HER2 expression and amplification are observed in ~15% of tumour biopsies from patients with a sensitising EGFR mutation who develop EGFR TKI resistance. It is unknown whether HER2 targeting in this setting can result in tumour responses. METHODS: A single arm phase II study was performed to study the safety and efficacy of trastuzumab and paclitaxel treatment in patients with a sensitising EGFR mutation who show HER2 expression in a tumour biopsy (IHC ≥ 1) after progression on EGFR TKI treatment. Trastuzumab (first dose 4 mg/kg, thereafter 2 mg/kg) and paclitaxel (60 mg/m2) were dosed weekly until disease progression or unacceptable toxicity. The primary end-point was tumour response rate according to RECIST v1.1. RESULTS: Twenty-four patients were enrolled. Nine patients were exon 21 L858R positive and fifteen exon 19 del positive. Median HER2 IHC was 2+ (range 1–3). For 21 patients, gene copy number by in situ hybridisation could be calculated: 5 copies/nucleus (n = 9), 5–10 copies (n = 8), and >10 copies (n = 4). An objective response was observed in 11/24 (46%) patients. Highest response rates were seen for patients with 3+ HER2 IHC (12 patients, ORR 67%) or HER2 copy number ≥10 (4 patients, ORR 100%). Median tumour change in size was 42% decrease (range −100% to +53%). -
Changing the Destiny of HER2 Expressing Solid Tumors
International Journal of Molecular Sciences Review Trastuzumab Deruxtecan: Changing the Destiny of HER2 Expressing Solid Tumors Alice Indini 1 , Erika Rijavec 1 and Francesco Grossi 2,* 1 Medical Oncology Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy; [email protected] (A.I.); [email protected] (E.R.) 2 Medical Oncology Unit, Department of Medicine and Surgery, University of Insubria, ASST dei Sette Laghi, 21100 Varese, Italy * Correspondence: [email protected] or [email protected] Abstract: HER2 targeted therapies have significantly improved prognosis of HER2-positive breast and gastric cancer. HER2 overexpression and mutation is the pathogenic driver in non-small cell lung cancer (NSCLC) and colorectal cancer, however, to date, there are no approved HER2-targeted therapies with these indications. Trastuzumab deruxtecan (T-DXd) is a novel HER2-directed antibody drug conjugate showing significant anti-tumor activity in heavily pre-treated HER2-positive breast and gastric cancer patients. Preliminary data have shown promising objective response rates in patients with HER2-positive NSCLC and colorectal cancer. T-DXd has an acceptable safety profile, however with concerns regarding potentially serious treatment-emergent adverse events. In this review we focus on the pharmacologic characteristics and toxicity profile of T-Dxd, and provide an update on the most recent results of clinical trials of T-DXd in solid tumors. The referenced papers were selected through a PubMed search performed on 16 March 2021 with the following searching terms: T-DXd and breast cancer, or gastric cancer, or non-small cell lung cancer (NSCLC), or colorectal cancer. -
Trastuzumab Emtansine (T-DM1)
Published OnlineFirst September 11, 2018; DOI: 10.1158/1078-0432.CCR-18-1590 Research Article Clinical Cancer Research Trastuzumab Emtansine (T-DM1) in Patients with Previously Treated HER2-Overexpressing Metastatic Non–Small Cell Lung Cancer: Efficacy, Safety, and Biomarkers Solange Peters1, Rolf Stahel2, Lukas Bubendorf3, Philip Bonomi4, Augusto Villegas5, Dariusz M. Kowalski6, Christina S. Baik7, Dolores Isla8, Javier De Castro Carpeno9, Pilar Garrido10, Achim Rittmeyer11, Marcello Tiseo12, Christoph Meyenberg13, Sanne de Haas14, Lisa H. Lam15, Michael W. Lu15, and Thomas E. Stinchcombe16 Abstract Purpose: HER2-targeted therapy is not standard of care Results: Forty-nine patients received T-DM1 (29 IHC 2þ, for HER2-positive non–small cell lung cancer (NSCLC). This 20 IHC 3þ). No treatment responses were observed in the phase II study investigated efficacy and safety of the HER2- IHC 2þ cohort. Four partial responses were observed in the targeted antibody–drug conjugate trastuzumab emtansine IHC 3þ cohort (ORR, 20%; 95% confidence interval, 5.7%– (T-DM1) in patients with previously treated advanced 43.7%). Clinical benefit rates were 7% and 30% in the IHC HER2-overexpressing NSCLC. 2þ and 3þ cohorts, respectively. Response duration for the Patients and Methods: Eligible patients had HER2-over- responders was 2.9, 7.3, 8.3, and 10.8 months. Median expressing NSCLC (centrally tested IHC) and received progression-free survival and overall survival were similar previous platinum-based chemotherapy and targeted between cohorts. Three of 4 responders had HER2 gene therapy in the case of EGFR mutation or ALK gene amplification. No new safety signals were observed. rearrangement. Patients were divided into cohorts based Conclusions: T-DM1 showed a signal of activity in patients on HER2 IHC (2þ,3þ). -
Trastuzumab Emtansine: a Novel Antibody-Drug Conjugate for HER2-Positive Breast Cancer
Author Manuscript Published OnlineFirst on October 17, 2013; DOI: 10.1158/1078-0432.CCR-13-0541 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Trastuzumab emtansine: a novel antibody-drug conjugate for HER2-positive breast cancer Ian Krop and Eric P Winer Dana-Farber Cancer Institute, Boston MA USA Running title: T-DM1 in HER2-positive breast cancer Corresponding author: Ian Krop Yawkey 1235 450 Brookline Ave, Boston MA 02215 [email protected] COI: IK: research support, Genentech, Consultant, GlaxoSmithKline and Genentech (uncompensated) EW: research support, Genentech 1 Downloaded from clincancerres.aacrjournals.org on September 25, 2021. © 2013 American Association for Cancer Research. Author Manuscript Published OnlineFirst on October 17, 2013; DOI: 10.1158/1078-0432.CCR-13-0541 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Abstract Trastuzumab emtansine (T-DM1) is a novel HER2-directed antibody-drug conjugate. T-DM1 consists of the potent anti-microtubule agent DM1, linked via a non-cleavable linker to the HER2-specific monoclonal antibody trastuzumab. Preclinical studies demonstrate that T-DM1 has dual mechanisms of action: selective delivery of DM1 to the HER2-positive tumor cell combined with trastuzumab’s activation of antibody-dependent cellular cytotoxicity and inhibition of HER2 mediated signal transduction. In phase 2 studies, T-DM1was active in patients with trastuzumab and lapatinib refractory metastatic breast cancer (MBC) and led to improved progression-free survival compared to the combination of trastuzumab and docetaxel in the first line setting. In a recent phase 3 trial in patients with MBC who previously received trastuzumab and a taxane, T-DM1 resulted in improved progression-free and overall survival compared to capecitabine and lapatinib. -
Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma
cancers Review Trastuzumab Mechanism of Action; 20 Years of Research to Unravel a Dilemma Hamid Maadi 1, Mohammad Hasan Soheilifar 2, Won-Shik Choi 1, Abdolvahab Moshtaghian 3,4 and Zhixiang Wang 5,* 1 Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB T6G 1Z2, Canada; [email protected] (H.M.); [email protected] (W.-S.C.) 2 Department of Medical Laser, Medical Laser Research Center, Yara Institute, ACECR, Tehran 1315795613, Iran; [email protected] 3 Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar 4741695447, Iran; [email protected] 4 Deputy of Research and Technology, Semnan University of Medical Sciences, Semnan 3514799442, Iran 5 Department of Medical Genetics and Signal, Transduction Research Group, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2H7, Canada * Correspondence: [email protected] Simple Summary: Overexpression of HER2 receptors have been identified in various types of cancer including breast cancer and ovarian cancer. HER2 overexpression is generally associated with poor clinical outcomes in patients with HER2-positve tumors. Trastuzumab, an antibody specifically targeting HER2 receptors, showed promising clinical benefits for patients with HER2-positive tumors. Studies show that trastuzumab suppresses HER2 receptors’ oncogenic functions in HER2-postive tumors. Moreover, trastuzumab has been shown to provoke immune responses against the HER2- amplified tumors. Citation: Maadi, H.; Soheilifar, M.H.; Choi, W.-S.; Moshtaghian, A.; Wang, Z. Trastuzumab Mechanism of Abstract: Trastuzumab as a first HER2-targeted therapy for the treatment of HER2-positive breast Action; 20 Years of Research to cancer patients was introduced in 1998. -
Abnormal Corneal Lesions Induced by Trastuzumab Emtansine: an Antibody–Drug Conjugate for Breast Cancer
CASE REPORT Abnormal Corneal Lesions Induced by Trastuzumab Emtansine: An Antibody–Drug Conjugate for Breast Cancer Mayuko Tsuda, MD,* Yoji Takano, MD,*† Chika Shigeyasu, MD,* Shigeru Imoto, MD, PhD,‡ and Masakazu Yamada, MD, PhD* been introduced.1 Trastuzumab emtansine (Kadcyla; Chugai Purpose: To report a case of atypical corneal lesions presumably Pharmaceutical Co., Ltd, Tokyo, Japan) is a new ADC induced by trastuzumab emtansine, an antibody–drug conjugate that is developed for the treatment of human epidermal growth designed to selectively deliver cytotoxic agents to human epidermal factor receptor 2 (HER2)–positive breast cancer.2 Trastuzu- growth factor receptor 2 (HER2)–positive breast cancer cells. mab emtansine received approval in 2013 in the United Case: A 64-year-old Japanese woman developed bilateral corneal States and the European Union and in 2014 in Japan. Breast epithelial abnormalities that originated from the limbus. The corneal cancers with overexpression of HER2 are associated with lesions covered the superior area in the right eye and both superior and a higher risk of recurrence with a shorter time to relapse, lower survival rates, and greater therapeutic resistance inferior areas including the visual axis in the left eye. The patient had 3,4 advanced ductal carcinoma of the left breast and had been receiving compared with HER2-normal disease. Trastuzumab, anticancer treatment with trastuzumab emtansine for 15 months. After a HER2-binding monoclonal antibody, alone stops growth switching the chemotherapy from trastuzumab emtansine monother- of cancer cells by binding to the HER2, whereas emtansine, a derivative of maytansine, enters the cells and destroys apy to the combination of docetaxel, trastuzumab, and pertuzumab, the 2 abnormal corneal lesions showed gradual improvement. -
EML) and Model List of Essential Medicines for Children (Emlc
Consideration of cancer medicines as part of the revisions to 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) Section 8 Immunomodulators and Antineoplastics This summary has been prepared by the Health Technologies and Pharmaceuticals (HTP) programme at the WHO Regional Office for Europe. It is intended to communicate changes to the 2019 WHO Model List of Essential Medicines for adults (EML) and Model List of Essential Medicines for children (EMLc) to national counterparts involved in the evidence-based selection of medicines for inclusion in national essential medicines lists (NEMLs), lists of medicines for inclusion in reimbursement programs, and medicine formularies for use in primary, secondary and tertiary care. This document does not replace the full report of the WHO Expert Committee on Selection and Use of Essential Medicines (see The selection and use of essential medicines: report of the WHO Expert Committee on Selection and Use of Essential Medicines, 2019 (including the 21st WHO Model List of Essential Medicines and the 7th WHO Model List of Essential Medicines for Children). Geneva: World Health Organization; 2019 (WHO Technical Report Series, No. 1021). Licence: CC BY-NC-SA 3.0 IGO: https://apps.who.int/iris/bitstream/handle/10665/330668/9789241210300-eng.pdf?ua=1) and Corrigenda (March 2020) – TRS1021 (https://www.who.int/medicines/publications/essentialmedicines/TRS1021_corrigenda_March2020. pdf?ua=1). Executive summary of the report: https://apps.who.int/iris/bitstream/handle/10665/325773/WHO- MVP-EMP-IAU-2019.05-eng.pdf?ua=1. The revised lists of essential medicines are available here: - World Health Organization Model List of Essential Medicines, 21st List, 2019. -
For Health Professionals Who Care for Cancer Patients
November 2013 Volume 16, Number 11 For Health Professionals Who Care For Cancer Patients Inside This Issue: . Editor’s Choice – New Programs: Pertuzumab with . Cancer Drug Manual – New: Romidepsin, Ruxolitinib; Trastuzumab and Docetaxel for Advanced Breast Cancer Revised: Tamoxifen (UBRAVPTRAD), Ruxolitinib for Symptomatic Myelofibrosis . Benefit Drug List – New: UBRAVPTRAD, ULKMFRUX; (ULKMFRUX); Highlights of Changes in Protocols, Pre‐ Deleted: GIFUINF Printed Orders and Patient Handouts: Eligibility Criteria for . List of New and Revised Protocols, Provincial Pre‐ CML Protocols Revised to Reflect Updated Guidelines Printed Orders and Patient Handouts – New: . Drug Update – Update: Shortage of Pegylated Liposomal ® UBRAVPTRAD, ULKMFRUX; Revised: GIAJFL, GIAVFL, Doxorubin (CAELYX ); Trastuzumab: Look‐Alike/Sound‐ GICART, UGIGAVCCT, GUAVPG, ULKCMLD, LKCMLI, Alike Medication Alert ULKMCLN, ULYBENDR, PUCAT, SAVAC; Deleted: . Continuing Professional Development – International GIFUINF Symposium on Oncology Pharmacy Practice (ISOPP) 2014 . Website Resources and Contact Information EDITOR’S CHOICE NEW PROGRAMS Breast: Pertuzumab with Trastuzumab and Docetaxel for First‐Line Treatment of Advanced HER2‐Positive Breast Cancer (UBRAVPTRAD) – The Breast Tumour Group has approved dual anti‐HER2 treatment with pertuzumab and trastuzumab in combination with docetaxel for the first‐line treatment of metastatic HER2‐positive breast cancer. This regimen is given every three weeks, with pertuzumab and trastuzumab continuing until disease progression or -
HER2-Targeted Immunotherapy and Combined Protocols Showed Promising Antiproliferative Effects in Feline Mammary Carcinoma Cell-Based Models
cancers Article HER2-Targeted Immunotherapy and Combined Protocols Showed Promising Antiproliferative Effects in Feline Mammary Carcinoma Cell-Based Models Andreia Gameiro, Catarina Nascimento , Jorge Correia and Fernando Ferreira * CIISA—Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal; [email protected] (A.G.); [email protected] (C.N.); [email protected] (J.C.) * Correspondence: [email protected]; Tel.: +351-21-365-2800 (ext. 431234) Simple Summary: Mammary tumors are common in cats, presenting an aggressive behavior with high tumor recurrence. Therefore, new and efficient therapeutic protocols are urgent. Monoclonal antibodies (mAbs; ADC) are widely used in human breast cancer therapy, inhibiting the HER2 dimerization and leading to cell apoptosis. Furthermore, drug combinations, with tyrosine kinase inhibitors (TKi) are valuable in patients’ therapeutic protocols. In this study, two mAbs, and an ADC, as well as combined protocols between mAbs and mAbs plus lapatinib (TKi) were tested to address if the drugs could be used as new therapeutic options in feline mammary tumors. All the compounds and the combined treatments revealed valuable antiproliferative effects, and a conserved cell death Citation: Gameiro, A.; Nascimento, mechanism, by apoptosis, in the feline cell lines, where the mutations found in the extracellular C.; Correia, J.; Ferreira, F. domain of the HER2 suggest no immunotherapy resistance. HER2-Targeted Immunotherapy and Combined Protocols Showed Abstract: Feline mammary carcinoma (FMC) is a highly prevalent tumor, showing aggressive Promising Antiproliferative Effects in clinicopathological features, with HER2-positive being the most frequent subtype. While, in human Feline Mammary Carcinoma breast cancer, the use of anti-HER2 monoclonal antibodies (mAbs) is common, acting by blocking the Cell-Based Models.